Non classical carbene ligands and their coordination chemistry

BENZIMIDAZOLE-BASED NON-CLASSICAL CARBENE LIGANDS AND THEIR COORDINATION CHEMISTRY ONG HONG LEE (B.Sc(Hons.), NUS) A THESIS SUBMITTED FOR THE DEGREE OF MASTER OF SCIENCE DEPARTMENT OF CHEMISTRY NATIONAL UNIVERSITY OF SINGAPORE 2010 Acknowledgements First and foremost, I would like to express my deepest gratitude to my Project Supervisor and mentor, Assistant Professor Huynh Han Vinh, for his kind guidance, tireless support and limitless patience. I am very fortunate to be under his tutelage, for in addition to chemistry, I have learnt a great deal about writing, presentation skills, research ethics and being a better person in general. For educating me above and beyond the call of duty, I owe him a debt of gratitude. I would also like to thank my lab mates – Dr. Han Yuan, Dr. Jothibasu and Yuan Dan for their kind guidance, assistance and useful discussions throughout my time in the lab and beyond. I would like to extend my thanks to the administrative and CMMAC staff – Ms. Suriawati, Mdm. Lai, Mdm. Wong, Ms. Tan, Mdm. Hong, Mdm. Han and Mr. Wong for their diligence and kindness in providing technical assistance, as well as NUS for the research scholarship. This project would not be manageable without the support and companionship from my precious friends – among them: Jun Wei, Zeff, Rong Lun, Justin, Terence Loh, Terence Lee, Erwin, Mel, Angela, Ivan, Chee Fei, Geck Woon and Tiffany. Last but not least, I would like to thank my family members – my mother Chong Hong, always patient; my dad Ah Kiat, always supportive; my sister Hong Nie, always caring – and my relatives, particularly my aunts – Mdm. Ong Bee Yian, Ms. Ong Ah Ngo and Ms. Ong Wah Ngoo – who have supported and helped me in countless ways throughout my academic pursuits. I am truly privileged to have my life graced with the presence of these benevolent characters and wish that our journeys together do not ever end. I Table of Contents Summary IV Chart 1. Compounds Synthesized in This Work VI List of Tables VIII List of Figures IX List of Schemes X XII List of Abbreviations 1 2 3 4 Introduction 1 1.1 Definition of Carbenes 1 1.2. Carbenes as Ligands in Metal Complexes 3 1.3. “Classical” N-Heterocyclic Carbenes 4 1.4. “Non-classical” N-Heterocyclic Carbenes 8 1.5. Synthesis of “Non-classical” N-Heterocyclic Carbenes 10 1.6. Aim and Objective 12 Palladium(II) Complexes bearing R2-2Ph-bim Ligands 15 2.1. Synthesis and Characterization of Ligand Precursors 15 2.2. Synthesis and Characterization of Palladium(II) complexes 18 A Palladium(II) Complex bearing a R2-2Me-bim Ligand 27 3.1. Synthesis and Characterization of Ligand Precursors 27 3.2. Synthesis and Characterization of Palladium(II) complexes 31 Catalytic Activity of Complex 15 36 4.1. 36 4.2. Catalytic Activity of 15 in the Buchwald- Hartwig Amination reaction Catalytic activity of 15 in the Sonogashira Coupling Reaction 38 II 5 Conclusions 43 6 Experimental 45 Appendix 60 References 62 III Summary This thesis deals with the synthesis, characterization and catalytic studies of organometallic palladium compounds bearing ligands which are potentially remote N-heterocyclic carbenes. The findings of this research are detailed in three chapters. Chapter 2 describes the synthesis and characterization of the proligand salts 2-(4-bromophenyl)-1,3-diethylbenzimidazolium tetrafluoroborate (Et2-2Ph-bim- Br)+BF4- (6), 3-benzyl-2-(4-bromophenyl)-1-ethylbenzimidazolium tetrafluoroborate (EtBn-2Ph-bim-Br)+BF4- (7), 1,3-dibenzyl-2-(4-bromophenyl)benzimidazolium tetrafluoroborate (Bn2-2Ph-bim-Br)+BF4- (8) as well as their corresponding palladium(II) complexes [PdBr(Et2-2Ph-bim)(PPh3)2]+BF4- (9), [PdBr(EtBn-2Phbim)(PPh3)2]+BF4- (10), [Pd Br(Bn2-2Ph-bim)(PPh3)2]+BF4- (11). The proligand salts were synthesized via alkylation of the two nitrogen atoms in the 2-(4bromophenyl)benzimidazole core. The palladium(II) complexes were synthesized via oxidative addition to tetrakis(triphenylphosphine)palladium(II). Analysis on the nature of the ligands in question as carbenes using molecular structural data revealed that complexes 9-11 may not be remote N-heterocyclic carbene complexes. Chapter 3 details the synthesis and characterization of the 6-bromo-1,3-dibenzyl2-methylbenzimidazolium tetrafluoroborate proligand (Bn2-2Me-bim-Br)+BF4- (14) and the corresponding palladium(II) complex [PdBr(Bn2-2Me-bim)(PPh3)2]+BF4(15). 14 was synthesized via alkylation with benzyl bromide on the two nitrogen atoms in the 6-Bromo-2-methylbenzimidazole core. The palladium(II) complex 15 was synthesized via oxidative addition to tetrakis(triphenylphosphine)palladium(II). We expect complex 15 to display carbene characteristics based on a comparison of IV spectroscopic data with an existing carbene complex of similar nature. However, spectroscopic analysis is not ample proof to conclude carbene formation and further studies, such as computational calculations, are required. In Chapter 4, the catalytic activity of complex 15 was tested in the BuchwaldHartwig amination reaction and the Sonogashira coupling reaction. 15 was active in both reactions, but gave disappointing yields for the former, while moderately well for the latter, giving quantitative yields for activated substrates. Most of the new compounds synthesized in this work have been characterized by multinuclei NMR, ESI mass spectrometry and X-ray diffraction analyses. These compounds are depicted in Chart 1. V Chart 1. Compounds synthesized in this work H N N Br Br N N 2 1 N N N Br N Br Br N - 3 Br 5 N N Br Br N BF4- 6 N N BF4- Br- 4 N N Br N - Br N BF4- BF4- 7 PPh3 Pd Br PPh3 N N BF4- 8 PPh3 Pd Br PPh3 N N BF4- 9 10 PPh3 Pd Br PPh3 11 VI VII List of Tables Table 2.1. Comparison of 13C{1H} NMR data 22 Table 2.2. Selected bond lengths (Å) and bond angles (°) for of 25 9·4CH3OH, 10·½C4H10O and 11·3CH3OH Table 4.1. Buchwald-Hartwig Amination Reactions Catalyzed by 15 38 Table 4.2. Sonogashira coupling reactions catalyzed by 15 40 Table 4.3. Sonogashira coupling reactions catalyzed by 15 42 VIII List of Figures Figure 1.1 Frontier orbitals and possible electronic configurations for 2 carbene carbon atoms Figure 1.2. Electronic configurations of sp2-hybridized carbenes 2 Figure 1.3. The first example of a Fischer Carbene 4 Figure 1.4. The first example of a Schrock Carbene 4 Figure 1.5. The three types of “classical’ NHC 5 Figure 1.6. Representative electronic interactions and resonance 7 structures of NHCs Figure 1.7. The Second Generation Grubb’s catalyst 8 Figure 1.8. Some examples of abnormal NHCs 8 Figure 1.9. Examples of remote carbenes 9 Figure 2.1. The two major portions of the proposed ligand and its 16 coordination site Figure 2.2. Molecular structure of 6 20 Figure 2.3. Two possible resonance structures of palladium(II) 21 complexes 9-11 Figure 2.4. The p-orbital overlaps in the carbene complex would 23 constrain the ligand in a rigid, planar geometry. Figure 2.5. Molecular structures of 9·4CH3OH, 10·½C4H10O and 24 11·3CH3OH Figure 3.1. Molecular structure of 14 30 Figure 3.2. Molecular structure of 15 33 IX List of Schemes Scheme 1.1. Wanzlick’s attempt at isolating free NHC 5 Scheme 1.2. Arduengo’s synthesis of the first stable NHC 6 Scheme 1.3. Canonical valence bond representations of an abnormal 9 NHC Scheme 1.4. Abnormal NHC complex synthesis by in-situ deprotonation 10 of azolium salts Scheme 1.5. Abnormal NHC complex synthesis via transmetallation 11 Scheme 1.6. Remote NHC complex synthesized via oxidative addition 11 Scheme 1.7. Remote NHC complex synthesized via heteroatom 12 alkylation Scheme 1.8. Abnormal NHC complex synthesized via cycloaddition to a 12 Fischer carbene complex Scheme 1.9. The proposed R2-2Ph-bim ligand system 13 Scheme 1.10. The proposed R2-2Me-bim ligand system 14 Scheme 2.1. Synthesis of the ligand precursor salts 16 Scheme 2.2. Mechanism for the formation of 1 17 Scheme 2.3. Synthesis of palladium(II) complexes by oxidative addition 20 Scheme 3.1. The designed ligand system and possible resonance 28 structures of the resulting complex Scheme 3.2. Synthesis of the ligand precursor salt 29 Scheme 3.3. Synthesis of the palladium(II) complex by oxidative 32 addition X Scheme 3.4. Attempted synthesis of procarbene complexes 16a/b 34 Scheme 3.5. Synthesis of complex 16c 35 Scheme 4.1. The Buchwald-Hartwig amination reaction 37 Scheme 4.2. The Sonogashira coupling reaction 39 Scheme 4.3. Synthesis of compound 16 via Sonogashira Coupling 41 XI List of Abbreviations Anal. Calc. Analysis calculated Ar Aryl br Broad Bn Benzyl ca About (Latin circa) d Doublet (NMR) / day dd Doublet of doublet (NMR) DME Dimethoxyethane DMF Dimethylformamide DMSO Dimethylsulfoxide δ NMR chemical shift e.g. For example (Latin exempli gratia) Equiv. Equivalent(s) ESI Electrospray ionization Et Ethyl et al. And others (Latin et alii) etc. And so on (Latin et cetera) h Hour I Inductive effect J Coupling constant m Multiplet (NMR) M Mesomeric effect XII min Minute MS Mass spectrometry m/z Mass to charge ratio NMR Nuclear Magnetic Resonance RT Room temperature s Singlet (NMR) t Triplet (NMR) THF Tetrahydrofuran XIII Chapter 1. Introduction 1.1 Definition of Carbenes Carbenes are neutral compounds containing a divalent carbon atom with six valence electrons. A carbene can be described as an organic molecule with the general formula RR’C:, in which the carbene carbon atom contains a pair of nonbonding electrons and is covalently bonded to two other atoms. Depending on the degree of hybridization, the geometry at the carbene carbon atom can either be bent or linear. When a carbene centre is sp-hybridized with two nonbonding energetically degenerate p-orbitals( the px and py orbitals), the linear geometry is adopted. On the other hand, when the carbene carbon atom is sp2hybridized, the bent geometry is adopted. Upon transition from the sp- to sp2hybridization, the energy of pπ remains relatively unchanged while the newly formed sp2-hybrid orbital, noted as σ, is energetically stabilized as it acquires partial s character (Figure 1.1). Most carbenes contain a sp2- hybridized carbene centre, hence linear carbenes are rarely observed. Four conceivable electronic configurations for the carbene centre are available: a triplet ground state (3B1) in which the two nonbonding electrons occupy the two different orbitals with parallel spins (σ1pπ1), two different singlet ground states (1A1 state) in which two nonbonding electrons are paired with antiparrallel spins in the same σ or p orbital (σ2pπ0 and σ0pπ2) and an excited singlet state (1B1) with antiparallel occupation of the σ and p orbitals (σ1pπ1).1 1 py linear px p 3 B1( p p bent 1 A1( p Figure 1.1 Frontier orbitals and possible electronic configurations for carbene carbon atoms1a Figure 1.2. Electronic configurations of sp2-hybridized carbenes. The reactivity and properties of carbenes are fundamentally determined by their ground-state spin multiplicity.2 Singlet carbenes contain a filled and an empty orbital and thus exhibit ambiphilic character. Triplet carbenes are considered diradicals as they have two orbitals with unpaired electrons. The multiplicity of the ground state is related to the energy gap between the σ and pπ orbitals. A Large energy difference in excess of 2 eV would stabilize a singlet ground state, leading to a singlet carbene while a smaller energy gap of less than 1.5 eV would lead to a triplet ground state. Steric and electronic effects brought about by the substituents at the carbene carbon 2 atom are known to influence the relative energy of the two orbitals and in turn influence the multiplicity of the ground state.3 For example, electron withdrawing substituents, which inductively stabilize the σ orbital by enriching its s character while leaving the pπ orbital relatively unchanged, increases the energy gap between the σ and pπ orbitals and thus favour the singlet state. On the other hand, electron donating groups decrease the energy gap between the two orbitals and stabilize the triplet state. Apart from inductive effects, mesomeric effects of the substituents also play a significant role. When the carbene carbon is attached to π-electron withdrawing group such as COR, CN, CF3 BR2 or SiR3, the triplet state is favoured. Likewise, if the carbene atom is attached to π-electron donating groups like N, O, P, S or halogens, the energy of the pπ orbital is increased, thus favouring the singlet state. 1.2 Carbenes as Ligands in Metal complexes The first example of a metal complex incorporating a carbene ligand was reported by Fischer in 1964.4 A double bond is drawn from the carbon donor atom to the metal centre due to the two types of interaction between the metal and the ligand: σdonation from the lone pair of the carbon to an empty metal d-orbital and π-back bonding of a filled orbital on the metal to the empty p-orbital of the carbon In this class of carbene complexes, the substituents on the carbon donor are π-donating, such as O or N. The metal centres usually consist of middle to late transition metals in a 3 low oxidation states. This class of complexes also contains π-acceptor co-ligands such as CO. In this case, the reactivity of the carbene carbon atom is electrophillic. Figure 1.3. The first example of a Fischer Carbene In a later study, Schrock reported a second class of metal carbene complexes – the Schrock carbenes.5 The carbon donor atoms in this type of complexes do not contain π-donating substituents, while the metal centres are early transition metals in high oxidation states. Schrock carbenes are nucleophillic, and are in the singlet state. Ta Figure 1.4. The first example of a Schrock Carbene 1.3 “Classical” N-Heterocyclic Carbenes A special class of Fischer carbene that has caught much attention lately is the Nheterocyclic carbene (NHC). In NHCs, the carbene carbon atom is incorporated into a heterocyclic ring. The classical representation of this type of ligands describes the carbon donor atom as being flanked by two nitrogen atoms in a five-membered heterocyclic ring. The heterocyclic ring can be saturated (imidazolidin-2-ylidenes, A), 4 unsaturated (imidazolin-2-ylidenes, B), or benzannulated (benzimidazolin-2-ylidenes, C). A: Imidazolidin-2-ylidene B: Imidazolin-2-ylidene C: Benzimidazolin-2-ylidene R N R N N R N R Figure 1.5. The three types of “classical” NHC. NHCs were initially studied by Wanzlick in the year 1962, when he reported the elimination of chloroform from an imidazoline derivative (Scheme 1.1, A). Unfortunately, the proposed imidazolin-2-ylidene (Scheme 1.1, B) could not be isolated and characterized as it dimerized into the corresponding enetetramine (Scheme 1.1, C). 6 Wanzlick further substantiates the formation of NHCs by trapping them as transition metal complexes7. Scheme 1.1. Wanzlick’s attempt at isolating free NHC. However, NHC chemistry remained relatively unexplored until the first stable free NHC was successfully isolated and spectroscopically characterized by Arduengo et. 5 al in 1991.8 Arduengo and co-workers obtained the first stable free NHC via the deprotonation of the corresponding imidazolium salt using sodium hydride as a base in the presence of a catalytic amount of DMSO in THF (Scheme 1.2). The stability of this type of bent singlet carbenes can be accounted by two factors: the mesomeric (M) and inductive (I) effects, collectively known as the “push-pull effect”. The +M effect ‘pushes’ the lone pair electrons from the N atoms into the vacant pπ orbital of the carbene carbon atom, while the –I effect of the σ-electron withdrawing N atoms ‘pulls’ electrons from the carbene center. These two effects bring about an increment in the energy gap between the σ and pπ orbitals, thus stabilizing the singlet carbene. Figure 1.6 shows a pictorial representation of the electronic interactions and their resonance structures. Scheme 1.2. Arduengo’s synthesis of the first stable NHC Arduengo’s discovery sparked interest in NHC chemistry, and as a result rapid development in the syntheses and applications of NHCs followed. In particular, NHC metal complexes found extensive application in the field of catalysis. Studies on the properties of NHCs revealed that NHCs are strong σ-donors and relatively poor π- 6 acceptors, similar to trialkylphosphines,9 which are widely used as ligands in metal catalysts. In fact, studies showed that NHCs are even more Lewis basic than electron rich phosphines and can potentially improve the stability and performance of well established catalytically active metal-phosphine complexes. X X X X X X X X X X X = NR Figure 1.6. Representative electronic interactions and resonance structures of NHCs.1 In light of this, many successful examples of the application of NHC complexes in organic transformations have been developed. Among them are: a) olefin metathesis catalyzed by ruthenium NHC complexes; b) C-C and C-N cross coupling reactions catalyzed by palladium NHC complexes; c) hydrosilylation of alkenes and alkynes catalyzed by Pt(0) NHC complexes; d) oligomerization and polymerization catalyzed by nickel NHC complexes; e) hydrogenation of alkenes and alkynes catalyzed by iridium or rhodium NHC complexes. The most notable of these studies is perhaps the development of the second generation Grubb’s catalyst, (Figure 1.7) which contributed to him being awarded the Nobel Prize in Chemistry in 2005. Substitution of a tricyclohexyl phosphine ligand in the first generation Grubb’s catalyst with a 7 NHC ligand led to a significant improvement in the stability of the catalyst for olefin metathesis reactions. N Cl Cl N Ru Ph PCy3 Figure 1.7. The Second generation Grubb’s catalyst 1.4 “Non-Classical” N-Heterocyclic Carbenes While most research on the topic of NHCs has been centered on the Arduengotype carbenes, where the carbene carbon atom is stabilized by two adjacent nitrogen atoms, there has been increasing interest in extending the NHC concept in different directions. In light of this, two new concepts of NHCs with less heteroatom stabilization have emerged in the recent years: the abnormal NHC concept and the remote NHC (rNHC) concept. Abnormal NHCs refer to NHCs for which a canonical valence bond representation requires the introduction of additional formal charges on some nuclei (Scheme 1.3).10 In most cases, these carbenes are only adjacent to one heteroatom (Figure 1.8). Figure 1.8. Some examples of abnormal NHCs. 8 Scheme 1.3. Canonical valence bond representations of an abnormal NHC. On the other hand, remote NHCs refer to carbenes which are stabilized by remote heteroatoms. This class of carbenes differ from the classical NHCs since they contain no heteroatom at the position α to the carbene centre. In this case, the heteroatom can be located within the same ring as the carbenoid carbon (Figure 1.9, A-C) or in an adjacent ring (Figure 1.9, D and E).11 N A B N C D N E Figure 1.9. Examples of remote carbenes. Experimental and theoretical studies have shown that carbene ligands with less heteroatomic stabilization are not only more donating than classical NHCs, but also show better activity in certain catalytic reactions.10 9 1.5 Synthesis of “Non-Classical” N-Heterocyclic Carbenes With the rising interests in “non-classical” NHC chemistry, a number of known methods have been developed for the synthesis of remote and abnormal NHC complexes. An overview of a few known methods is outlined below: a) In situ deprotonation of azolium salts. This method is more commonly used as a route to abnormal NHC complexes rather than remote carbene complexes. It involves the deprotonation of an acidic procarbene proton of an azolium salt either by suitable external bases or metal complexes with a basic ligand. For instance, the diimidazolium salt (Scheme 1.4) is deprotonated by the basic acetate ligands from Pd(OAc)2 to form the corresponding abnormal NHC complex.12 I- N N N Pd(OAc)2 N DMSO, 120 C N I Pd N I- N I N Scheme 1.4. Abnormal NHC complex synthesis by in-situ deprotonation of azolium salts.13 b) Transmetallation of silver carbene complex. The transmetallation protocol, initially developed by Lin and co-workers for the preparation of classical NHC complexes,13 can also be extended to the synthesis of abnormal NHC complexes. This method makes use of Ag2O as a metal precursor to deprotonate the azolium salts to generate Ag-NHC complexes. Due to the labile Ag-Ccarbene bond, the Ag10 NHC complexes can act as transfer reagents to other metals such as Pd, Rh, Au and Ir. Scheme 1.5. Abnormal NHC complex synthesis via transmetallation.14 c) Oxidative addition. Initially reported by Stone in 1974,15 this method involves the oxidative addition of a C-X bond to a low oxidation-state metal precursor such as [Ni(COD)2] or [Pd(PPh3)4]. Both abnormal and remote NHC complexes have been synthesized in this manner.16,11 This method is the main protocol used to synthesize the metal complexes presented in this dissertation. Scheme 1.6. Remote NHC complex synthesized via oxidative addition.16d d) Heteroatom alkylation. In this method, a metal complex with a heterocyclic ligand can be alkylated at the heteroatom to generate a remote or abnormal carbene complex. For example, the aryl complex below is alkylated with a methyl substituent at the N atom to give rise to the corresponding rNHC complex.17 11 Scheme 1.7. Remote NHC complex synthesized via heteroatom alkylation. e) Cycloaddition to Fischer carbene complexes. Another alternative route to nonclassical NHC complexes is by the cycloaddition of dinucleophiles to unsaturated Fischer-type carbenes. For example, the pyrazolylidene complex below was obtained upon addition of dimethylhydrazine to the alkynyl carbene.18 Scheme 1.8. Abnormal NHC complex synthesized via cycloaddition to a Fischer carbene complex. 1.6 Aim and Objective Due to the interesting properties and applications of rNHC complexes, we would like to extend our studies in this field by investigating rNHC complexes with the heteroatom and carbene carbon located in separate rings. Thus far, only two examples of such carbene complexes have been synthesized by Raubenheimer et. al. recently, derived from the quinoline systems.18 In the R2-2Ph-bim system (R = alkyl), we prepared a ligand precursor which consists of a benzimidazolium salt with an aryl ring at the C2 position. At the other 12 end of this aryl ring, a C-Br bond allows oxidative addition which gives access to the corresponding palladium complex (Scheme 1.8). The intended carbon donor atom would be 5 bonds away from the heteroatoms and the ring containing the carbene carbon and the heterocycle are only connected by one C-C bond. A structural analysis of the ligand’s geometry in the metal complex can draw distinction on whether the ligand acts as a zwitterionic ligand (Scheme 1.8, B) or a neutral carbene. In the carbene form, the system should be conjugated with alternating double bonds which would result in a planar geometry (Scheme 1.8, A). On the other hand, if the ligand acts as a zwitterionic aryl ligand, the C-C bond between the two rings would have free rotation, resulting in a non-linear geometry of the ligand due to steric repulsion between the two rings. The results and details of this study will be discussed in Chapter 2. R N L M X L N R A R N L M X L N R B Scheme 1.9. The proposed R2-2Ph-bim ligand system A second system, the R2-2Me-bim (R = alkyl) system studies the metallation of a benzimidazolium salt at the C6-position. Typically, in a ‘classical’ NHC complex, the metallation occurs at the C2 position. In this case, the C2 position of the ligand precursor is blocked by a methyl group and a C-X bond is located at the C6 position of the benzimidazolium salt. This enables us to perform an oxidative addition to the 13 C-X bond with Pd(0) to synthesize the complex. As above, this could either behave as a carbene complex (Scheme 1.9, A) or a zwitterionic aryl complex (Scheme 1.9, B). Although structural analysis of the resulting complex does not directly discern between these two forms, spectroscopic analysis have been performed in an attempt to address the ambiguity. Results and discussions on this system would be focused in Chapter 3. Bn N Bn N L N Bn M X L L N Bn M X L and other resonance structures A B Scheme 1.10. The proposed R2-2Me-bim ligand system Lastly, a preliminary investigation on the catalytic activity of a synthesized complex in the Buchwald-Hartwig amination reaction and the Sonogashira C-C coupling reaction is reported in Chapter 4. 14 Chapter 2: Palladium (II) Complexes bearing R2-2Ph-bim Ligands 2.1 Synthesis and Characterization of Ligand Precursors To investigate whether a carbene can be formed with only heteroatom stabilization from a separate ring, we envisioned a system which consists of two major portions, a benzimidazole portion (Figure 2.1, A) and a phenyl ring (Figure 2.1, B). The two rings are not fused together, unlike previous examples of such rNHC,17 but instead linked by a single C-C bond. The metal was to be coordinated on the carbon donor labeled X. In order to achieve this, oxidative addition was chosen as an approach to coordinate carbon X to palladium, as deprotonation on such a site would be challenging as the target proton may not be sufficiently acidic. Towards this end, a synthesis has been developed to prepare the corresponding ligand precursor with a CBr bond at the appropriate position (Scheme 2.1). For comparison purposes, we prepared three different ligand precursors: the 1,3-diethyl substituted salt 6, 1-ethyl-3benzyl substituted salt 7 and the 1,3-dibenzyl substituted salt 8. Starting from 1,2-phenylenediamine and 4-bromobenzaldehyde, a method developed by Bahrami et. al.19 was modified to achieve the large scale and high yield synthesis of 1. The mechanism for this reaction (Scheme 2.2) involves the formation of hypochlorous acid by the reaction of aqueous hydrogen peroxide with hydrochloric 15 acid,20 which then reacts with the cyclic hydrobenzimidazole A to afford the intermediate B followed by the abstraction of hydrogen to yield the corresponding 2aryl benzimidazole 1. The oxidation of chloride in the absence of catalyst is possible and has been previously reported.37 In contrast to other methods of preparing 2-aryl benzimidazoles, this method provides a simple and efficient route to 1 as the product readily precipitates from the reacting mixture, and workup is as simple as washing with water and ethyl acetate. Apart from that, high yields of up to 73% are attainable in reaction scales of up to 30 mmol of starting materials in only 3 hours of reaction time. X R N N R A B Figure 2.1. The two major portions of the proposed ligand and its coordination site. Scheme 2.1. Synthesis of the ligand precursor salts. 16 Scheme 2.2. Mechanism for the formation of 1.20 To generate the ligand precursor salts, the two N atoms on 1 were alkylated with alkyl bromides. The N-alkylation was performed stepwise since this method allows for easier separation of the desired products from by-products such as inorganic salts in each step. Also, the isolation of the monoalkylated intermediate 2 would prove useful for the synthesis of a salt with two different N-substituents. Initial attempts to alkylate the first N atom using 1 equivalent of sodium hydroxide and bromoethane in acetonitrile, an oft-used procedure for mono-alkylation of benzimidazoles,21 did not give satisfactory yields. The procedure resulted in a mixture of desired products, starting materials and unknown side products which were difficult to separate. Thus different combinations of conditions and solvents were screened to optimize the mono-alkylation of 1. It was found that the most feasible route involves using 4 equivalents of sodium hydroxide and 6 equivalents of 17 alkylating reagent in DMSO. Using bromoethane, 2 was obtained and isolated at 77% yield. The synthesis of 2 was confirmed by 1 H and 13 C NMR, as signals corresponding to the ethyl protons and carbons in the aliphatic range of the spectra were observed. The positive mode ESI mass spectrum showed a base peak at m/z = 301 corresponding to the [M + H]+ cation. 2 was then subjected to a second N-alkylation by bromoethane to give the diethyl bromide salt 3. The formation of 3 was supported by ESI mass spectrometry, as a signal at m/z = 330 corresponding to the cation [M - Br]+ was detected in the positive mode. Salt 4 was synthesized analogously from 2 using benzyl bromide. The formation of 4 was supported by 1H and 13C NMR, where signals characteristic to the benzyllic protons and carbons were detected in addition to the signals from its precursor. The positive mode ESI mass spectrum also showed a base peak at m/z = 391 corresponding to the [M - Br]+ cation. The 1,3-dibenzyl substituted salt 5 was synthesized from 1 using benzyl bromide for both alkylation steps. Similarly, multinuclei NMR and ESI mass spectrometry results indicate successful formation of the salt. The intermediate to 5, 2a was not isolated and characterized since the 1-benzyl-3-ethyl substituted salt 4 can already be prepared from 2. 2.2. Synthesis and Characterization of Palladium(II) Complexes In order to synthesize bis(phosphine) palladium(II) complexes, the bromide anions of the ligand precursors must first be replaced with non-coordinating anions. 18 This is done via reaction with sodium tetrafluoroborate to generate salts 6-8. The replacement of bromide anions by tetrafluoroborate anions were supported by ESI mass spectrometry, where the negative mode spectra for all three salts showed the disappearance of the signal at m/z = 79 corresponding to the Br- anion and the appearance of a new signal at m/z = 87 corresponding to the anion BF4-. The 19 F NMR spectra of compounds 6-8 also show the expected signals arising from the presence of the BF4- anion. As a representative of the three ligand precursors, salt 6 was crystallized to illustrate its molecular structure. X-ray diffraction analysis of the single crystals obtained from the slow evaporation of a saturated DCM solution revealed that 6 adopted a twisted geometry in the solid state as expected (Figure 2.2). The dihedral angle of the plane formed by the benzimidazole backbone portion of the molecule and the plane formed by the aryl ring measures 88.47°. The NCN bond lengths of 1.336(5) Å and 1.355(5) Å as well the NCN bond angle of 108.9(3)° are within the expected range of values for a benzimidazolium salt. The C1-C12 bond length is 1.466(6) Å, suggesting that the two major portions of the molecule are linked by a single C-C bond. The C-Br bond distance is 1.901(4) Å. The metal complexes were prepared by oxidative addition across the C-Br bonds of the ligand precursors (Scheme 2.3). Tetrakis(triphenylphosphine)palladium(0) was chosen as the metal precursor of choice as it affords the products in higher yields compared to other precursors such as Pd2(dba)3/PPh3, which resulted in lower yields and decomposition of the precursor before the product could be formed. This could be 19 due to the improved stability of [Pd(PPh3)4] as a metal source compared to the transient [Pd(PPh3)n] generated by the Pd2(dba)3/PPh3 system. Figure 2.2. Molecular structure of 6 showing 50% probability ellipsoids; hydrogen atoms and BF4- counter anion are ommited for clarity. Selected bond lengths [Å] and angles [°]: C15-Br1 1.901(4), C15-C16 1.385(7), C16-C17 1.361(7), C17-C12 1.373(6), C12-C13 1.380(6), C13-C14 1.388(6), C14-C15 1.371(7); N1-C1-N2 108.9(3), C1-N1-C2 108.5(3), C1-N2-C7 108.7(3). Scheme 2.3. Synthesis of palladium(II) complexes by oxidative addition. Treatment of [Pd(PPh3)4] with one equivalent of salts 6, 7 and 8 in refluxing dichloromethane led to the formation of cationic complexes 9, 10 and 11, 20 respectively. The removal of by-products by precipitating the reaction mixture with ether and subsequent washing with water afforded analytically pure 9, 10 and 11 in yields of 51%, 89% and 82%. The formation of complexes 9-11 were confirmed by base peaks in the positive mode ESI mass spectra at m/z = 961 (9), 1021 (10), and 1085 (11), respectively, corresponding to the [M - BF4]+ fragments. An analysis of the 1H NMR integral values of 9-11 suggests that there are two phosphine ligands to one carbon donor ligand. The phosphine donors in all three complexes resonate as singlets at similar positions in the 31 P NMR spectra with chemical shifts of 24.3 ppm (9, 10) and 24.2 ppm (11) each, indicating a trans arrangement of the phosphine ligands. In their 13C NMR spectra, the disappearance of a signal at ca 119 ppm (C-Br) and the appearance of a triplet at ca 170 ppm (Pd-C) indicated that metallation has occurred across the CBr bond of the precursors. The NCN signals in the 13C NMR spectra of 9-11 remain relatively unchanged compared to that of their precursors 6-8 at ca 151 ppm. Figure 2.3. Two possible structures of palladium(II) complexes 9-11 21 9-11 may be represented by two resonance structures: one illustrating a purely carbene complex (figure 2.3, b) and another illustrating a purely σ-aryl complex. While the true nature of these complexes may lie in between these two representations, investigating which structures the complexes most likely resemble might give us a clue as to whether 9-11 are more likely to behave as carbene complexes or σ-aryl complexes. In doing so, analysis of the 13C NMR spectra and the molecular structures of 9-11 could prove useful. Previous work on both classical1 and remote NHCs11 noted that upon complexation, the 13 C signal corresponding to the carbene carbon atom is significantly downfield shifted (in excess of 35 ppm) as compared to the 13 C NMR signal of the analogous carbon in its precursor. Table 2.1 summarizes a comparison of these 13C NMR signals in 8-11 and their precursors with a few examples in literature. Table 2.1. Comparison of 13C NMR data 13 Reference C NMR chemical shift of C donor atom / ppm 1 11b 2 3 Entry 4 5 6 Complex 9 10 11 13 ∆/ ppm 127.8 C NMR chemical shift of corresponding C in precursor / ppm 66.8 17 180.7 143.3 37.4 17 187.0 134.5 52.5 169.6 170.3 171.2 119.8 119.7 119.6 49.8 50.6 51.6 61.0 22 As shown in Table 2.1, the 13 C NMR resonance of the carbon donor atoms in complexes 9-11 gave rise to a ca 50 ppm downfield shift from their precursors. Thus, in this respect, complexes 9-11 show a similar characteristic as other carbene complexes. However, this method of determination of carbenes may be limited and arbitrary. Several factors, such as the position of the heteroatom(s), the substitution pattern, contribution from aromaticity, steric constraints or the nature of cispositioned ligands may influence the chemical shift substantially and limit the use of NMR as an efficient tool for carbene determination.22 To compliment the solution-state studies, the ligand system was designed to allow discrimination between the two complex types by analysis of their molecular structures. As shown on Figure 2.3, σ-aryl complexes would contain singly bonded C-C bridges between the two major segments of the ligands. Thus, the bonds are free to rotate and the ligands would adopt a ‘twisted’ structure due to the steric repulsion between the two cyclic structures (figure 2.3, a). However, if the complexes are carbene complexes, the resulting resonance structure would result in π-bonded bridges, with alternating double bonds on either side of the phenyl ring (Figure 2.3, b). We propose that the p-orbital overlaps would constrain the ligands to a rigid planar structure, where the benzimidazole backbone portion and the phenyl ring portion of the ligand lie in the same plane (figure 2.4). Figure 2.4. The p-orbital overlaps in the carbene complex would constrain the ligand in a rigid, planar geometry. 23 In preparation of this, single crystals of 9 and 11 were grown from the slow evaporation of saturated methanol solutions, while single crystals of 10 were obtained from the slow diffusion of ether into a saturated solution of 10 in acetonitrile. The molecular structures of 9·4CH3OH, 10·½C4H10O and 11·3CH3OH are shown in Figure 2.5, while their selected bond angles and bond lengths are listed in Table 2.2. Figure 2.5. Molecular structures of 9·4CH3OH (top left), 10·½C4H10O (top right) and 11·3CH3OH (bottom) showing 50% probability ellipsoids. Hydrogen atoms, solvent molecules and BF4- counter anions have been ommited for clarity. 24 Table 2.2 Selected bond lengths (Å) and bond angles (°) for of 9·4CH3OH, 10·½C4H10O and 11·3CH3OH Pd1-C1 Pd1-Br1 Pd1-P1 Pd1-P2 C1-C2 C2-C3 C3-C4 C4-C5 C5-C6 C6-C1 C4-C7 C7-N1 C7-N2 C1-Pd1-Br1 P1-Pd1-P2 C1-Pd1-P1 C1-Pd1-P2 P1-Pd1-Br1 P2-Pd1-Br1 9·4CH3OH 2.019(2) 2.5586(4) 2.3270(6) 2.3176(6) 1.377(3) 1.383(4) 1.390(4) 1.398(3) 1.380(4) 1.397(3) 1.475(4) 1.339(3) 1.335(3) 178.29(7) 176.66(3) 91.25(6) 91.36(6) 88.517(18) 88.821(19) 10·½C4H10O 2.012(6) 2.5375(9) 2.3401(18) 2.3099(18) 1.407(9) 1.384(10) 1.374(10) 1.382(10) 1.398(10) 1.371(9) 1.484(10) 1.326(9) 1.352(9) 171.96(18) 175.75(6) 92.27(19) 89.86(19) 91.40(5) 86.95(5) 11·3CH3OH 2.007(3) 2.5106(4) 2.3385(8) 2.3178(8) 1.393(4) 1.388(4) 1.388(4) 1.390(4) 1.390(4) 1.387(4) 1.478(4) 1.339(4) 1.344(4) 168.55(8) 167.84(3) 91.76(8) 88.82(8) 93.63(2) 88.04(2) Complexes 9-11 adopt square-planar geometries around their metal centers, as expected of palladium(II) complexes. The phosphine donors are arranged in a trans configuration with respect to each other, in agreement with the 31P NMR analysis in solution. More importantly, the molecular structure of 9-11 revealed that the ligands in question adopt a twisted geometry in line with structure type a (figure 2.3). The plane consisting of the aryl rings on the ligand and the plane generated by the benzimidazole backbones intersect at dihedral angles of 63.44 ° (9), 63.83 (10) and 60.23 (11), which are smaller than that observed in 8, possibly due to steric repulsion between the N-substituents and the phenyl groups on triphenylphosphine. The C4-C7 bond lengths measure at ca 1.48 Å, which comes closer to a C-C σ-bond. Apart from 25 that, the bond distances between each carbon of the ring containing the donor atom have values between a single and double C-C bond, concurring with those found in an aromatic ring. Although the determination of whether a complex can be termed as a true carbene complex or a complex with a zwitterionic ligand is not an easy and straightforward task, based on the data obtained from the molecular structures analysis, we can make an informed speculation that complexes 9-11 are more likely to behave as σ-aryl complexes rather than rNHC complexes. However, future work possibly involving computational calculations should be done to further substantiate this deduction. 26 CHAPTER 3: A Palladium(II) Complex Bearing a R2-2Mebim Ligand 3.1 Synthesis and Characterization of the Ligand Precursor As a continuation of our study on NHCs with reduced heteroatom stabilization, we extended our studies towards to an alternative benzimidazole ligand system. Benzimidazole-based NHC ligands are typically coordinating through the C2 carbon, leading to the established classical benzimidazolin-2-ylidenes. Inspired by advances made in the imidazole system, where blocking of the usual coordination site at the C2 carbon and coordinating a metal atom at the C4 or C5 carbon yields abnormal NHC complexes,10a we attempted a similar approach on the benzimidazole system. In this approach, the C2 carbon is blocked by a methyl moiety, and coordination at the benzene ring is made possible by oxidative addition to a C-Br bond (Scheme 3.1, A). A unique feature of such a ligand system is that upon complexation, several resonance structures are possible: the ligand could either exist as a σ-aryl zwitterionic ligand (Scheme 3.1, B-D) or as a carbene which is both ‘remote’ and ‘abnormal’ (scheme 3.1, G-H). In light of this, we have devised a synthetic protocol starting with 4-bromo-1,2diaminobenzene and acetic acid (Scheme 3.2). The C2 blocked benzimidazole 12 was synthesized in 81% yield via refluxing 4-bromo-1,2-diaminobenzene in glacial acetic acid. The formation of the organic compound was confirmed by ESI mass spectrometry, where a signal at m/z = 211 corresponding to the [M + H]+ fragment 27 Scheme 3.1. The designed ligand system and possible resonance structures of the resulting complex. was found in the positive mode spectrum. The first N-alkylation was done via the deprotonation of the NH proton followed by the addition of benzyl bromide to 1. This process yielded an inseparable mixture of isomeric mono-alkylated benzimidazoles, a and b (scheme 3.2) at a combined yield of 88%. Their identities were confirmed by their positive mode ESI mass spectrum, which contained a base peak at m/z = 301 corresponding to their [M + H]+ cations. The 1H NMR spectrum of the mixture showed two benzyllic proton signals, each corresponding to one isomer, at 5.35 and 5.33 ppm with almost equal integrals, suggesting that the products formed at a 1:1 ratio. Due to the difficulty in separating the two isomers, the mixture was subjected to a second N-alkylation with the same alkylating reagent to generate the homosubstituted bromide salt 13. The positive mode ESI mass spectrum of 13 shows a base peak at m/z = 391 corresponding to the [M - Br]+ cation. Also worth noting was that the C6 carbon resonates at 120.4 ppm in the 13 C NMR spectrum, a value typical in aromatic C-Br groups. In preparation for the formation of diphosphine 28 palladium(II) complexes, the bromide anion in salt 13 was exchanged with sodium tetrafluoroborate in methanol. This yielded salt 14 in 61% yield. The replacement of bromide anions by tetrafluoroborate anions was supported by ESI mass spectrometry, where the negative mode spectra for 14 showed the disappearance of the signal at m/z = 79 corresponding to the Br- anion and the appearance of a new signal at m/z = 87 corresponding to the anion BF4-. The 19F NMR spectra of compound 14 also showed the expected signals arising from the presence of the BF4- anion. The 13 C and 1H NMR spectra of compound 14 remain largely unchanged compared to those of compound 13. Scheme 3.2. Synthesis of the ligand precursor salt. Single crystals of 14 were subjected to X-ray crystallographic analysis to elucidate its molecular structure. Figure 3.2 shows the molecular structure of 14. The backbone of the benzimidazole backbone formed a plane while the two N-substituents are 29 arranged syn to each other, pointing out of the plane. The N-C bond lengths of 1.334(10) Å and 1.341(9) Å as well the NCN bond angle of 109.0(7)° are within the expected range for a disubstituted benzimidazolium salt. Similarly, the C-C bonds of the fused benzene ring reflect those of a typical benzimidazolium salt. The C5-Br1 bond length of 1.878(7) Å is typical of an aromatic C-Br bond. Figure 3.1. Molecular structure of 14 showing 50% probability ellipsoids; disordered atoms, hydrogen atoms and the BF4- counter anion are ommited for clarity. Selected bond lengths [Å] and angles [°]: C1-C8 1.486(11), C1-N1 1.334(10), C1-N2 1.341(9), N1-C2 1.388(9), N2-C7 1.383(9), C2-C7 1.364(10), C2-C3 1.428(11), C3C4 1.306(10), C4-C5 1.391(11), C5-C6 1.410(10), C6-C7 1.365(10), C5-Br1 1.878(7); N1-C1-N2 109.0(7), C1-N1-C2 108.1(6), C1-N2-C7 108.7(6). 30 3.2 Synthesis and Characterization of the Palladium(II) Complex The synthesis of the palladium(II) complex 15 was achieved by refluxing 14 and tetrakis(triphenylphosphine)palladium(0) in dichloromethane (Scheme 3.3). Concentration of the reaction mixture and subsequent precipitation with ether led to a white powder, which contained crude 15. Due to its low solubility in THF, analytically pure 15 can be obtained as a white solid by precipitation from a saturated THF solution at room temperature. Comparison of the signal integrals from the benzyllic protons to the aromatic protons in the 1H NMR of 15 revealed a ratio of 4:43, indicating that the complex consists of two triphenylphosphine ligands, one carbon donor ligand and a bromido ligand. In the 13 C NMR spectrum, the carbon donor atom resonates at 159.5 ppm as a triplet with a coupling constant of 2J(P,C) = 4.42 Hz. The 31 P NMR spectrum of 15 contains a single resonance at 25.1 ppm, suggesting that the two phosphine donors are arranged trans to each other. Signals at -76.64 and -76.68 ppm in the 10 19 F NMR spectrum of 15 indicated the presence of BF4- and 11BF4- counter anions, which suggest the formation of a cationic palladium complex. Moreover, the positive mode ESI mass spectrum showed a base peak at m/z = 1023 corresponding to the [M - Br]+ cation. The identity of the product was further confirmed by X-ray diffraction analysis on the single crystals of 15. The molecular structure of 15 is shown in Figure 3.3. As expected, the geometry around the metal centre is a distorted square plane. The carbocycle containing the carbon donor lies almost perpendicular to the coordination plane, intersecting at a dihedral angle of 89.77°. The Pd-C1 distance of 1.986(10) Å 31 offers little insight into whether 15 is a carbene complex, since CCSD data23 show little distinction in Pd-C or Pd-X bond lengths between known trans(aryl)(PPh3)2PdX and trans-(NHC)(PPh3)2PdX (X= Br, Cl) examples. Apart from that, the C-C/C=C bond lengths of the carbocycle containing the carbon donor atom showed little distinction from the bond lengths of a bicyclic σ-aryl ligand. Despite this observation, it has been noted by Raubenheimer et. al. that molecular structural data were not useful probes to confirm or dismiss carbene formation based on their findings in a similar quinolin-based system.17 Scheme 3.3. Synthesis of the palladium(II) complex by oxidative addition. As mentioned in the previous chapter, comparison of the 13C NMR spectra could also shed some light on whether 15 is a carbene complex. Upon complexation with palladium, the carbon donor atom resonates at 159.5 ppm. In comparison to the analogous carbon in the precursor salt 14, a downfield shift of 38.8 ppm occurs upon complexation. This downfield shift is similar to Raubenheimer’s findings in a transchloro-(1,2-methyl-1,7-dihydroisoquionlin-7-ylidene)bis(triphenylphosphine) palladium(II) triflate complex (Table 2.1, entry 2), where a downfield shift of 37.4 ppm was recorded.17 The N heteroatom in the aforementioned system is 3 bonds away 32 from the carbene carbon and located in a separate ring, thus in principal bearing close similarity with the complex 15. Figure 3.2. Molecular structure of 15 showing 50% probability ellipsoids; Hydrogen atoms and the BF4- counter anion omitted for clarity. Selected bond lengths [Å] and angles [°]: Pd1-C1 1.986(10), Pd1-P1 2.325(3), Pd1-P2 2.321(3), Pd1-Br1 2.5180(13), C1-C2 1.336(15), C2-C3 1.419(14), C3-C4 1.342(15), C4-C5 1.413(15), C5-C6 1.369(14), C6-C1 1.451(15), C3-N2 1.423(13), N2-C7 1.316(14), C7-N1 1.379(15), N1-C4 1.386(13), C7-C22 1.473(14); C1-Pd1-Br1 172.5(4), P1-Pd1-P2 174.45(11), C1-Pd1-P1 86.6(3), C1-Pd1-P2 89.8(3), P1-Pd1-Br1 91.57(8), P2-Pd1Br1 92.57(8). A more direct method to identify carbene formation would be through synthesizing procarbene complexes 16a/b (Scheme 3.4). Comparison of the 13C NMR resonance of the carbon donor atom in the procarbene complexes with that of the assumed carbene carbon in 15 would allow us to verify carbene formation. If a severe 33 Scheme 3.4. Attempted synthesis of procarbene complexes 16a/b. difference exists between the resonance of the carbon donor atoms of 16a/b and 15, while the other carbons resonances are relatively similar, carbene formation can be assumed.17 A synthesis of complexes 16a/b was attempted from the inseparable mixture of monoalkylated benzimidazole a/b with tetrakis(triphenylphosphine)palladium(0). However, the complexes 16a/b could not be successfully synthesized. The reaction mixture led to a mixture of unknown products, which identities could not be determined by multinuclei NMR and ESI mass spectrometry. The isolation of any products from the mixture also proved to be unfeasible as the mixture readily decomposes to palladium black upon separation attempts by crystallization, chromatography or solubility. This result could be due to the fact that a total of four or more products were present due to the possibility of Ccoordination and N-coordination to palladium. In a further attempt to rationalize our assumption that 15 is a carbene complex, we synthesized the complex 16c from the reaction of 4-bromobenzaldehyde and tetrakis(triphenylphosphine)palladium(0) (Scheme 3.5).24 As 16c is clearly not a carbene complex, we can confirm if a similar downfield shift as mentioned above also occurs in σ-aryl complexes. The carbon donor in 16c resonates at 174.3 ppm in the 13 C NMR spectrum, which is 44.6 ppm downfield shifted from the analogous carbon 34 in 4-bromobenzaldehyde. This downfield shift is considerably larger in magnitude than that observed in 15, perhaps illustrating the different nature of the two ligand systems. However, this also shows that observing a severe downfield shift in the resonance of the carbon donor upon complexation is not an ample proof to confirm carbene formation as NMR shifts can still be affected by a variety of factors. Scheme 3.5. Synthesis of complex 16c. While the comparison with Raubenheimer’s results allows us to expect 15 to behave as a rNHC complex, analysis of 16c proved that it is difficult to determine whether a complex behaves as σ-aryl complex or rNHC complex only by spectroscopic analysis. Thus, future investigations, either in the form of analyzing other derivatives of 15 or computational calculation, are required in this respect to gauge the true nature of complex 15. 35 Chapter 4: Catalytic Activity of Complex 15 4.1 Catalytic Activity of 15 in the Buchwald-Hartwig Amination Reaction The palladium(II) complex 15 was first tested for its performance in the Buchwald-Hartwig amination reaction.25 This reaction involves the C-N coupling between an aryl halide and an amine in the presence of base and a metal catalyst (Scheme 4.1). A number of palladium(II) complexes, including those incorporating two phosphine ligands and a NHC ligand, have been known to perform efficiently as precatalysts in this reaction.26 Thus it is in our interest to investigate the activity of complex 15 in the Buchwald-Hartwig amination reaction. The catalytic cycle of the Buchwald-Hartwig amination reaction is initiated when a palladium(II) precatalyst complex is reduced to an active palladium(0) species. Loss of a ligand leads to the active palladium(0) species (Scheme 4.1,A). The cycle then starts with an aryl halide coordinating to the active species by oxidative addition (Scheme 4.1, B). Ligand substitution of the halide with the amine then leads to the formation of intermediate C. A strong base then deprotonates the amine to form the intermediate D, which undergoes reductive elimination to give the desired C-N coupling product. The liberated palladium(0) species then continues the cycle with another aryl halide. 36 Scheme 4.1. The Buchwald-Hartwig amination reaction. 3-bromopyridine and morpholine are chosen as substrates to screen for suitable conditions for the amination. Among the commonly used solvents for this reaction, DME proved to be the most effective solvent (Table 4.1, entry 1), although only 17% yield was obtained. In our next attempt to optimize the reaction, we varied the base used to deprotonate the amine (Table 4.1, Entries 1,5-7). Only strong bases KOtBu (Table 4.1, entry 1) and NaOtBu (Table 4.1, entry 5) gave quantifiable yields, with KOtBu being the better of the two. In our final attempt to improve yield, we decided to increase the reaction temperature to 100 °C (Table 4.1, entries 8-9). However, even 37 at an elevated temperature and a prolonged reaction time of 48 h (table 4.1, entry 9), the maximum yield obtained was only 22%. Thus, it was evident that although complex 15 does promote the Buchwald-Hartwig amination reaction, it is not a very effective and efficient catalyst. Table 4.1. Buchwald-Hartwig amination reactionsa catalyzed by 15 Br NH + N O 15 O N base, solvent N Entry Solvent Base t [h] Temp [°C] Yield [%]b t 1 DME KO Bu 24 50 17 2 THF KOtBu 24 50 15 t 3 Toluene KO Bu 24 50 8 4 1,4-Dioxane KOtBu 24 50 Trace 5 DME NaOtBu 24 50 4 6 DME NaOAc 24 50 Trace DME 24 50 Trace 7c t 8 DME KO Bu 24 100 19 9 DME KOtBu 48 100 22 a Reaction conditions: 1 mmol of 3-bromopyridine; 1.2 mmol of morpholine; 2ml of solvent; 1.5 equiv of base; 1 mol% of 15. b isolated yields. c 6 equiv of morpholine used as base. 4.2. Catalytic Activity of 15 in the Sonogashira Coupling Reaction. Despite the poor performance of 15 in the Buchwald-Hartwig amination reaction, we continued to test the performance of 15 in the catalytic Sonogashira coupling reaction. In general, Sonogashira coupling refers to the C-C coupling of terminal alkynes with aryl or vinyl halides (Scheme 4.2).27 Typically, this class of reaction is catalyzed by palladium and a copper salt as co-catalyst. The generally accepted mechanism is shown in Scheme 4.2. 38 Overall Reaction: 1 + R X 2 H R Catalytic Cycle: Pd cat., (Cu+ cat.) R1 NR3 R1 = aryl, hetaryl, vinyl R2 = aryl, hetaryl, alkyl, SiR3 X = I, Br, Cl, OTf PdIIL2X2 R1 R2 R2 R1 X Pd0L2 L 1 R Pd L Palladium Cycle R Cu+X- H L R Pd X L 1 2 R2 Cu Copper Cycle R3N+HX- R2 Cu R2 Cu+X- NR3 Scheme 4.2. The Sonogashira coupling reaction. The mechanism is thought to involve two independent catalytic cycles: the palladium cycle and the copper cycle. The palladium cycle is based on a usually fast oxidative addition of an aryl or vinyl halide (R1X) to the active catalyst generated from the initial palladium complex. This is commonly thought to be a palladium(0) species, formed by reduction of the precatalyst under the employed reaction conditions. It is known that n-electron donors, such as phosphines, amines, and 39 ethers, used as ligands and solvents, can reduce palladium(II) species typically via σcomplexation-dehydropalladation-reductive elimination. The next step in the palladium cycle connects with the copper cycle, which involves a transmetallation from the copper-acetylide formed in the copper cycle to generate a R1Pd(─C≡CR2)L2 species. Finally, a trans/cis isomerization occurs and reductive elimination leads to the release of the final coupled alkyne with regeneration of the catalyst. In the copper cycle, the base, typically an amine, abstracts the acetylenic proton of the terminal alkyne to form the copper acetylide complex in the presence of the copper(I) salt. Amine bases are typically thought to be insufficiently basic to abstract a free acetylenic proton, thus it is thought that a π-alkyne-Cu complex forms prior to the deprotonation. Transmetallation with the palladium complex in the palladium cycle then regenerates the initial copper(I) salt. Table 4.2. Sonogashira coupling reactionsa catalyzed by 15 Entry Aryl Halide t [h] Temp [°C] Yield [%]b 1 4-bromobenzaldehyde 1 80 >99 2 4-bromoacetophenone 3 80 >99 3 4-bromotoluene 24 80 76 4 4-bromoanisole 24 80 40 5 24 80 63c 2 6 4-chlorobenzaldehyde 24 80 8 a Reaction conditions: 1 mmol of aryl halide; 2 mmol of phenylacetylene; 1.2 mmol of NEt3; 5 mol% of CuI; 1 mol% of 15; 1 ml degassed of DMF. b Yields were determined by 1H NMR spectroscopy for an average of two runs. c Isolated yield. 40 Scheme 4.3. Synthesis of compound 16 via Sonogashira Coupling. By employing standard conditions and a catalyst loading of 1 mol%, complex 15 prove to be a suitable catalyst precursor leading to quantitative yields for activated aryl bromides (Table 4.2, entries 1-2). Coupling of electron-rich aryl bromides resulted in good to moderate yields (Table 4.2, entries 3-5). It is worth noting that the coupling of 2 with phenylacetylene led to the formation of novel compound 17 at a yield of 63% (Table 4.2, entry 5/Scheme 4.3). The coupling of phenylacetylene with 4-chlorobenzaldehyde resulted in very low yield (Table 4.2, entry 6), accentuating the limitations of 15 in catalyzing the coupling of aryl chlorides. In light of recent advancements in copper and amine-free Sonogashira coupling reactions,27b,c we attempted the coupling of 4-bromobenzaldehyde and phenylacetylene using similar conditions. However, satisfactory results could not be obtained as the reactions attempted with 15 as catalyst gave incomplete conversions, side products and undesired homocoupling products. In a separate study, the influence of catalyst loading on the Sonogashira Coupling reaction catalyzed by 15 was investigated (Table 4.3). At a catalyst loading of 1 mol% the coupling of 4-bromobenzaldehyde with phenylacetylene reached completion within an hour (Table 4.3, entry 1). Further lowering of the catalyst loading led us to discover that at a catalyst loading of 0.02 mol%, a maximum turnover number of 3800 could be reached by increasing the reaction time to 72 h 41 (table 4.3, entry 5). Increasing reaction temperature is unfavourable as yield values dropped when an elevated temperature of 120 °C was applied (Table 4.3, entry 6). Further reduction of catalyst loading resulted in only trace amounts of products being formed (Table 4.3, entries 7-8). Table 4.3. Sonogashira coupling reactionsa catalyzed by 15 Entry [Pd] [mol%] t [h] Temp [°C] Yield [%]b TON 1 1 1 80 >99 100 2 0.5 24 80 >99 200 3 0.2 24 80 91 455 4 0.2 30 80 >99 500 5 0.02 72 80 76 3800 6 0.02 72 120 51 2850 7 0.002 72 80 trace 0 8 0.002 72 80 trace 0 a Reaction conditions: 1 mmol of 4-bromobenzaldehyde; 2 mmol of phenylacetylene; 1.2 mmol of NEt3; 5 mol% CuI; 1 ml of degassed DMF. b Yields were determined by 1 H NMR spectroscopy for an average of two runs. Although the performance of 15 in the Sonogashira reaction pales in comparison to highly efficient phosphine catalyst systems like the Na2[PdCl4]/PtBu328, ferrocenylphosphine29 and tetraphosphane30 systems, we are hopeful as a TON of 3800 is comparatively high for NHC-based catalysts.27b Modifications to the coligands, metal centre or counter anion could possibly improve the performance and robustness of the catalyst and would prove to be a useful and interesting subject for future efforts. 42 Chapter 5: Conclusions The synthesis, characterization and carbene characteristic of the palladium(II) complexes bearing ligands derived from the 2-(4-bromophenyl)benzimidazole (2Phbim-Br) system and the 6-bromo-2-methylbenzimidazole (2Me-bim-Br) system were investigated in this work. A condensation reaction between 1,2-phenylenediamine and 4- bromobenzaldehyde led to the formation of the 2-(4-bromophenyl)benzimidazole core (2Ph-bim-Br) (1). N-alkylations on the 2Ph-bim-Br core with bromoethane and benzyl bromide led to the dialkylated bromide salts (Et2-2Ph-bim-Br)+Br- (3), (EtBn2Ph-bim-Br)+Br- (4), and (Bn2-2Ph-bim-Br)+Br- (5). 3-5 were subjected to salt metathesis to generate the tetrafluoroborate salts (Et22Ph-bim-Br)+BF4- (6), (EtBn2Ph-bim-Br)+BF4- (7) and (Bn2-2Ph-bim-Br)+BF4- (8). Oxidative addition of 6-8 to tetrakis(triphenylphosphine)palladium(0) resulted in the formation of palladium(II) complexes [PdBr(Et2-2Ph-bim)(PPh3)2]+BF4- (9), [PdBr(EtBn-2Ph-bim)(PPh3)2]+BF4(10) and [PdBr(Bn2-2Ph-bim)(PPh3)2]+BF4- Investigation of the molecular structure of 9-11 also showed that they are more likely σ-aryl complexes rather than rNHC complexes. However, future work such as computational calculations is required to confirm the true nature of the R2-2Ph-bim ligands. The core structure of the second system we studied, 6-bromo-2- methylbenzimidazole (2Me-bim) (12), was prepared by condensation of 4-bromo-1,2diaminobenzene with acetic acid. This compound was then doubly N-alkylated with benzyl bromide to form the bromide salt (Bn2-2Me-bim-Br)+Br- (13). 13 was 43 converted to a suitable ligand precursor (Bn2-2Me-bim-Br)+BF4- (14) via salt metathesis with sodium tetrafluoroborate. Oxidative tetrakis(triphenylphosphine)palladium(0) led to [PdBr(Bn2-2Me-bim)(PPh3)2]+BF4- 15 is (15). the addition of palladium(II) thought to display 14 to complex carbene characteristic since the carbon donor atom encounters a downfield shift of 38.8 ppm upon complexation, matching values of a known and proven rNHC ligand. However this conclusion is based on limited evidence as it is proven that a large downfield shift in the resonance of the carbon donor is not an ample proof to confirm carbene formation. Future efforts to endeavor other methods such as the preparation and analysis of other derivatives or theoretical calculations should be considered to further substantiate this conclusion. The catalytic activity of 15 was tested in the Buchwald-Hartwig amination reaction and the Sonogashira coupling reaction. 15’s performance in the BuchwaldHartwig amination reaction prove to be disappointing, as only a yield of 22% could be obtained despite efforts to optimize reaction conditions. On the other hand, 15 performed relatively well in the Sonogashira coupling reaction, giving a quantitative yield for the coupling of activated aryl bromides and good to moderate yields for the coupling of deactivated aryl bromides. However, 15 is limited by its inability to catalyze the coupling of aryl chlorides. Apart from that, the dependency of 15 on anaerobic conditions and copper salts to successfully catalyze the coupling reactions brings forth another limitation of the catalyst. The applicability of 15 as an effective catalyst in other organic reactions remains as a subject for future endeavours. 44 Chapter 6: Experimental General Considerations Unless otherwise noted all operations were performed without taking precautions to exclude air and moisture. All solvents and chemicals were used as received without any further treatment if not noted otherwise. CH2Cl2 was dried with CaH2 and distilled under nitrogen using Tetrakis(triphenylphosphine)palladium(0), standard Schlenk techniques. 4-Bromo-1,2-diaminobenzene and 4- bromobenzaldehyde were received from Alfa Aesar. 1,2-phenylenediamine was received from Sigma-Aldrich. 1H, 13 C, 31 P, and 19 F NMR spectra were recorded on Bruker ACF 300 and AMX 500 spectrometers, and the chemical shifts (δ) were internally referenced to the residual solvent signals relative to tetramethylsilane (1H, 13 C) or externally to 85% H3PO4 (31P) and CF3CO2H (19F). Mass spectra were measured using a Finnigan MAT LCQ (ESI) spectrometer. Elemental analyses were performed on a Perkin-Elmer PE 2400 elemental analyzer at the Department of Chemistry, National University of Singapore. 2-(4-Bromophenyl)benzimidazole (1) Compound 1 was synthesized via a slight modification to of H N Br N literature procedure.19 1,2-phenylenediamine (3.246 g, 30.0 mmol) and 4-bromobenzaldehyde (5.554 g, 30.0 mmol) was dissolved in 15 mL of CH3CN in a 100 mL rbf fitted with a reflux condenser. 18 mL of 35% H2O2 and 8.8 mL of 37% HCl was added to the flask through the condenser successively with 45 stirring. The resulting mixture was allowed to stir for an additional 3 hours. The mixture was then filtered, and the crude product was washed a few times with H2O and ethyl acetate. The remaining solid was dried under vacuum to yield 1 as a reddish-brown powder (5.988 g, 21.9 mmol, 73 %). Analytical data of this compound was identical with literature values.31 2-(4-Bromophenyl)-1-ethylbenzimidazole (2) To a suspension of 1 (1.365 g, 5.0 mmol) in DMSO (15 N Br mL), 4 equivalents of NaOH (3.20 mL, 20 mmol, 6.25 M) N was added. The resulting mixture was stirred for 30 minutes before bromoethane (2.3 mL, 30.8 mmol) was added. The mixture was left to stir overnight at ambient temperature. After removing the volatiles and solvent in vacuo, the residue was suspended in H2O and the mixture was extracted with CH2Cl2 (3 x 30 mL). The combined organic extracts were washed with H2O (100 mL) and was concentrated down to 5-10 mL by evaporation under reduced pressure. This solution was then passed through a layer of silica gel. Evaporation of the solvent afforded 2 as a yellow powder (1.163 g, 3.86 mmol, 77 %). 1 H NMR (300 MHz, CDCl3): δ 7.86-7.85 (m, 1H, Ar-H), 7.70-7.60 (m, 4H, Ar-H), 7.46-7.42 (m, 1H, Ar-H), 7.35-7.32 (m, 2H, ArH), 4.28 (q, 3J(H,H) = 7.23 Hz, 2H, CH2), 1.48 (t, 3J(H,H) = 7.23 Hz, 3H, CH3). 13 C{1H} NMR (126 MHz, CDCl3): δ 152.8 (NCN), 143.3, 135.9, 132.8, 131.4, 129.8, 125.2, 123.8, 123.5 (Ar-C), 120.6 (C-Br), 110.7 (Ar-C), 40.4 (NCH2CH3), 16.0 (NCH2CH3). Anal. Calc. for C15H13BrN2: C, 59.82; H, 4.35; N, 9.30. Found: C, 59.87; H, 4.24; N, 9.07. MS (ESI): m/z = 301 [M + H]+. 46 2-(4-Bromophenyl)-1,3-diethylbenzimidazolium Bromide (3) In a rbf fitted with a reflux condenser, 2 (0.900 g, 3.0 N Br N Br - mmol) was dissolved in toluene (20 mL). Excess bromoethane (2.3 mL, 30.8 mmol) was added into the rbf and the mixture was heated under reflux for 60 hours. The precipitate formed was filtered off and washed with toluene to yield 3 (0.443 g, 1.08 mmol, 36%). 1H NMR (500 MHz, CDCl3): δ 7.88 (d, 2H, Ar-H), 7.86-7.85 (m, 4H, Ar-H), 7.66 (dd, 2H, ArH), 4.41 (q, 3J(H,H) = 7.55 Hz, 4H, CH2), 1.47 (t, 3J(H,H) = 7.55 Hz, 6H, CH3) . 13 C{1H} NMR (126 MHz, CDCl3): 149.4 (NCN), 134.2, 132.8, 131.8, 129.3, 128.2 (Ar-C), 120.3 (C-Br), 114.2 (Ar-C), 43.2 (NCH2CH3), 15.6 (NCH2CH3). Anal. Calc. for C17H18Br2N2: C, 49.78; H, 4.42; N, 6.83. Found: C, 49.49; H, 4.46; N, 6.78. MS (ESI): m/z = 330 [M - Br]+, 79 [Br]-. 3-Benzyl-2-(4-Bromophenyl)-1-Ethylbenzimidazolium Bromide (4) Compound 4 was synthesized analogously to 3 from 2 (0.900 g, 3.0 mmol) and benzyl bromide (3.6 mL, 30.3 N Br N Br - mmol). Yield: 1.290 g (2.73 mmol, 91%). 1H NMR (500 MHz, CDCl3): δ 7.95-7.93 (m, 2H, Ar-H), 7.87-7.85 (m, 1H, Ar-H), 7.80-7.78 (m, 2H, Ar-H), 7.65-7.62 (m, 2H, Ar- H), 7.57-7.55 (m, 1H, Ar-H), 7.30-7.29 (m, 3H, Ar-H), 7.08-7.07 (m, 2H, Ar-H), 5.62 (s, 2H, CH2Ph), 4.44 (q, 3J(H,H) = 7.55 Hz, 2H, CH2CH3), 1.51 (t, 3J(H,H) = 7.55 Hz, 3H, CH3). 13 C{1H} NMR (126 MHz, CDCl3): 150.4 (NCN), 134.0, 133.8, 133.0, 132.6, 131.8, 130.0, 129.5, 129.3, 128.3, 128.2, 127.5 (Ar-C), 120.3 (C-Br), 114.9, 47 114.2 (Ar-C), 51.5 (NCH2Ph), 43.3 (NCH2CH3), 15.6 (NCH2CH3). Anal Calc. for C22H20Br2N2: C, 55.96; H, 4.61; N, 4.28. Found: C, 55.83; H, 4.02; N, 5.91. MS (ESI): m/z = 391 [M - Br]+, 79 [Br]-. 1,3-Dibenzyl-2-(4-Bromophenyl)benzimidazolium Bromide (5) To a suspension of 1 (1.365 g, 5.0 mmol) in DMSO (15 mL), 4 equivalents of NaOH (3.20 mL, 20 mmol, 6.25 M) N Br N Br - was added. The resulting mixture was stirred for 30 minutes before benzyl bromide (3.6 mL, 30.3 mmol) was added. The mixture was left to stir overnight at ambient temperature. After removing the volatiles and solvent in vacuo, the residue was suspended in H2O and the mixture was extracted with CH2Cl2 (3 x 30mL). The combined organic extracts were washed with H2O (100 mL) and the solvent was removed in vacuo. The resulting residue was dissolved in toluene (30 mL), and another portion of benzyl bromide (6 mL, 50.4 mmol) was added. The reaction mixture was heated under reflux for 60 hours. The precipitate formed was filtered off and washed with toluene to yield 5 (1.925 g, 3.60 mmol, 72%). 1H NMR (300 MHz, DMSO-d6): δ 7.99 (dd, 2H, Ar-H), 7.96 (d, 2H, Ar-H), 7.81 (d, 2H, Ar-H), 7.70 (dd, 2H, Ar-H), 7.34-7.31 (m, 6H, Ar-H), 7.22-7.19 (m, 4H, Ar-H), 5.61 (s, 4H, NCH2). 13 C{1H} NMR (76 MHz, DMSO-d6): δ 150.2 (NCN), 133.8, 132.8, 132.4, 131.3, 128.7, 128.3, 127.3, 127.2, 127.1 (Ar-C), 120.1 (C-Br), 114.1 (Ar-C), 49.3 (NCH2Ph). Anal Calc. for C27H22Br2N2: C, 60.70; H, 4.15; N, 5.24. Found: C, 60.33; H, 4.23; N, 5.05. MS (ESI): m/z = 453 [M - Br]+, 79 [Br]-. 48 2-(4-Bromophenyl)-1,3-Diethylbenzimidazolium Tetrafluoroborate (6) 3 (0.410g, 1 mmol) was dissolved in a minimal amount of N Br N BF4 - acetone. NaBF4 (0.440g, 4.0 mmol) was added to the solution and the mixture was stirred overnight. The reaction mixture was filtered through Celite, and the solvent of the filtrate was removed in vacuo. The remaining solid was dissolved in CH2Cl2 and filtered through Celite. Removal of the solvent in vacuo afforded the product (0.318 g, 0.76 mmol, 76%). Crystals suitable for X-ray diffraction studies were obtained by the slow evaporation of a concentrated solution of 6 in CH2Cl2. 1H NMR (300 MHz, CD2Cl2): δ 7.84-7.82 (m, 4H, Ar-H), 7.75-7.72 (m, 2H, Ar-H), 7.64-7.60 (m, 2H, Ar-H), 4.30 (q, 3J(H,H) = 7.32 Hz, 4H, CH2), 1.42 (t, 3J(H,H) = 7.32 Hz, 3H, CH3). 13C{1H} NMR (75.5 MHz, CD2Cl2): δ 148.9 (NCN), 133.9, 131.7, 131.3, 128.7, 127.8 (Ar-C), 119.8 (C-Br), 113.5 (Ar-C), 42.2 (NCH2), 14.8 (CH3). 19 F{1H} NMR (282.4 MHz, CD2Cl2): δ - 77.67 (s, 10BF4), -77.71 (s, 11BF4). Anal Calc. for C17H18BBrF4N2: C, 48.96; H, 4.35; N, 6.72. Found: C, 49.16; H, 4.18; N, 6.58. MS (ESI): m/z = 329 [M - BF4]+, 87 [BF4]-. 3-Benzyl-2-(4-Bromophenyl)-1-Ethylbenzimidazolium Tetrafluoroborate (7) NaBF4 (1.098 g, 10 mmol) was added into a solution of 4 (0.479 g, 1 mmol) in methanol (10 mL). The mixture was N Br N BF4 - stirred at room temperature over a period of 4 days. The solvent of the reaction mixture was then removed in vacuo and CH2Cl2 (20 mL) was added to residue. The suspension 49 was then filtered through Celite to remove the excess NaBF4 and the solvent of the filtrate was removed in vacuo, leaving 7 as a white solid. Yield: 0.360 g (7.51 mmol, 75%). 1H NMR (300 MHz, CD2Cl2): δ 7.90-7.82 (m, 3H, Ar-H) 7.72-7.60 (m, 5H, Ar-H) 7.32-7.30 (m, 3H, Ar-H) 7.09-7.05 (m, 2H, Ar-H) 5.51 (s, 2H, CH2Ph) 4.37 (q, 3 J(H,H) = 7.41 Hz, 2H, CH2CH3) 1.46 (t, 3J(H,H) = 7.41 Hz, 3H, CH3). 13C NMR (76 MHz, CD2Cl2): δ 149.7 (NCN), 133.7, 133.2, 131.9, 131.8, 131.3, 129.5, 129.1, 128.8, 127.9, 127.7, 127.1 (Ar-C), 119.7 (C-Br) 114.1, 113.6 (s, Ar-C), 50.3 (CH2Ph), 42.5 (CH2CH3) 14.8 (CH3). 19F NMR (282 MHz, CD2Cl2): δ -77.38 (s, 10BF4), -77.43 (s, 11 BF4). Anal Calc. for C22H20BBrF4N2: C, 55.15; H, 4.21; N, 5.85. Found: C, 55.57; H, 3.96; N, 5.85. MS (ESI) m/z = 391 [M - BF4]+, 87 [BF4]-. 1,3-Dibenzyl-2-(4-Bromophenyl)benzimidazolium Tetrafluoroborate (8) Compound 8 was synthesized analogously to 7 from 4 (0.535 g, 1.0 mmol). Yield: (0.370 g, 68%). 1H NMR (300 N Br N BF4 - MHz, CD2Cl2): δ 7.78-7.54 (m, 8H, Ar-H) 7.34-7.32 (m, 6H, Ar-H), 7.10-7.07 (m, 4 H, Ar-H) 5.56 (s, 4 H, CH2Ph). 13 C NMR (75 MHz, CD2Cl2): δ 150.7 (NCN), 133.7, 133.1, 132.1, 131.9, 129.6, 129.2, 129.0, 128.0, 127.1 (Ar-C), 119.6 (C-Br), 114.2 (Ar-C), 50.6 (CH2Ph). 19 F NMR (282 MHz, CD2Cl2): δ -77.27 (s, 10 BF4), -77.33 (s, 11 BF4). Anal Calc. for C27H22BBrF4N2: C, 59.92; H, 4.10; N, 5.18. Found: C, 59.80; H, 4.02; N, 5.06. MS (ESI) m/z = 453 [M - BF4]+, 87 [BF4]-. 50 [PdBr(Et2-2Ph-bim)(PPh3)2]+BF4- (9) 6 (0.083 g, 0.2 mmol) and [Pd(PPh3)4] (0.230 g, 0.2 PPh3 Pd Br PPh3 N N BF4 - mmol) was added into a two neck rbf fitted with a reflux condenser under an atmosphere of nitrogen. Anhydrous CH2Cl2 (10 mL) was added into the flask and the reaction mixture was refluxed under nitrogen overnight shielded from light. The reaction mixture was then concentrated down to a few mL, and added dropwise into a rbf of diethyl ether (100 mL) with vigorous stirring. The precipitate formed was filtered and washed with diethyl ether (2 x 50 mL). The residue was then dissolved in CH2Cl2 (20 mL) and washed with water (3 x 20 mL). The remaining solution was dried in vacuo to yield 9 (0.106 g, 1.01 mmol, 51%). Crystals suitable for X-ray diffraction studies were obtained by the slow evaporation of a concentrated solution of 9 in cold methanol. 1H NMR (500 MHz, CD2Cl2): δ 7.82 (dd, 2H, Ar-H), 7.72-7.67 (m, 14H, Ar-H), 7.48-7.45 (m, 8H, Ar-H), 7.41-7.38 (m, 12H, Ar-H), 6.55-6.53 (m, 2H, Ar-H), 4.00 (q, 3J(H,H) = 7.60 Hz, 4H, CH2), 1.44 (t, 3J(H,H) = 7.60 Hz, 6H, CH3). 12 C{1H} NMR (126 MHz, CD2Cl2): δ 169.6 (t, 2J(P,C) = 4.13 Hz, C-Pd), 150.6 (s, NCN), 138.4 (t, 2/3 J(P,C) = 4.60 Hz, Ar-C), 135.0 (t, 2/3J(P,C) = 5.97 Hz, Ar-C), 132.2 (s, Ar-C), 131.6 (t, 1J(P,C) = 23.42 Hz, Ar-C), 131.2 (s, Ar-C), 130.7 (s, Ar-C), 128.4 (t, 2/3J(P,C) = 5.05 Hz, ArC), 127.6 (s, Ar-C), 127.2 (s, Ar-C), 113.8 (s, Ar-C), 113.6 (s, Ar-C), 42.1 (s, NCH2), 15.1 (s, CH3). 11 BF4). 31 19 F{1H} NMR (282 MHz, CD2Cl2): δ -77.58 (s, 10 BF4), -77. 63 (s, P{1H} NMR (202 MHz, CD2Cl2): δ 24.3 (2P, PPh3). Anal Calc. for C53H48BBrF4N2P2Pd: C, 60.74; H, 4.62; N, 2.67. Found: C, 60.82; H, 4.47; N, 2.67. MS (ESI) m/z = 961 [M - BF4]+. 51 [PdBr(EtBn-2Ph-bim)(PPh3)2]+BF4- (10) Compound 10 was synthesized analogously to 9 from 7 N N BF4 - PPh3 Pd Br PPh3 (0.096 g, 0.02 mmol). Yield: (0.198 g, 0.18 mmol, 89%). Crystals suitable for X-ray diffraction studies were obtained by the slow diffusion of ether into a concentrated solution of 10 in acetonitrile. 1H NMR (500 MHz, CD2Cl2): δ 7.84-7.75 (m, 1H, Ar-H) 7.68-7.57 (m, 13H, Ar-H) 7.51-7.45 (m, 1H, Ar-H) 7.42-7.25 (m, 24H, Ar-H) 7.06-6.99 (m, 2H, Ar-H) 6.61-6.53 (m, 2H, ArH) 5.14 (s, 2H, CH2Ph) 4.06 (q, 3J(H,H) = 7.15 Hz, 2H, CH2CH3) 1.47 (t, 3J(H,H) = 7.15 Hz, 3H, CH3). 12 C{1H} NMR (126 MHz, CD2Cl2): δ 170.3 (t, 2J(P,C) = 3.67 Hz, C-Pd) 151.6 (s, NCN), 138.4 (t, 2J(P,C) = 5.05 Hz, Ar-C), 135.1 (t, 2J(P,C) = 6.43 Hz, Ar-C), 133.5 (s, Ar-C), 131.6 (t, 1(P,C) = 23.4 Hz, Ar-C) , 131.5 (s, Ar-C), 131.3 (s, Ar-C), 130.6 (s, Ar-C), 129.7 (s, Ar-C), 129.2 (s, Ar-C), 128.3 (t, 2J(P,C) = 5.51 Hz, Ar-C), 127.6 (s, Ar-C), 127.5 (s, Ar-C), 127.4 (s, Ar-C), 126.7 (s, Ar-C), 114.4 (s, Ar-C), 113.6 (s, Ar-C), 50.4 (s, CH2Ph), 42.4 (s, CH2CH3), 15.1 (s, CH3). 19F{1H} NMR (282.4 MHz, CD2Cl2): δ -77.65 (s, 10 BF4), -77.71 (s, 11 BF4). 31 P{1H} NMR ( 202 MHz, CD2Cl2): δ 24.3 (2P, PPh3). Anal Calc. for C58H50BBrF4N2P2Pd : C, 62.75; H, 4.54; N, 2.52. Found : C, 63.00; H, 5.03; N, 2.26. MS (ESI) m/z = 1021 [M BF4]+. 52 [PdBr(Bn2-2Ph-bim)(PPh3)2]+BF4- (11) Compound 11 was synthesized analogously to 10 from 8 (0.108 g, 0.02 mmol). Yield: 0.192 g ( 0.164 mmol, PPh3 Pd Br PPh3 N N BF4 - 82%). Crystals suitable for X-ray diffraction studies were obtained by the slow evaporation of a concentrated solution of 9 in cold methanol. 1H NMR (500 MHz, CD2Cl2): 7.60-7.54 (m, 12H, Ar-H), 7.44-7.35 (m, 12H, Ar-H), 7.26-7.24 (m, 18H, Ar-H), 7.08-7.06 (m, 4H, Ar-H), 6.67-6.65 (m, 2H, Ar-H), 5.25 (s, 2H, CH2). 12 C{1H} NMR (126 MHz, CD2Cl2): δ 171.2 (t, 2J(P,C) = 3.67 Hz, C-Pd), 152.6 (s, NCN), 138.5 (t, 2/3 J(P,C) = 4.59 Hz, Ar-C), 135.1 (t, 2/3 J(P,C) = 6.43 Hz, Ar-C), 133.5 (s, Ar-C), 132.2 (s, Ar-C), 131.7 (s, Ar-C), 131.5 (t, 1J(P,C) = 23.87 Hz, Ar-C), 130.6 (s, Ar-C), 129.8 (s, Ar-C), 129.3 (s, Ar-C), 128.3 (t, 2/3J(P,C) = 5.05 Hz, Ar-C), 127.7 (s, Ar-C), 127.6 (s, Ar-C), 126.7 (s, Ar-C), 114.4, (s, Ar-C), 113.3 (s, Ar-C), 50.7 (s, CH2). 11 BF4). 31 19 F{1H} NMR (282.4 MHz, CD2Cl2): δ -77.46 (s, 10 BF4), -77.52 (s, P{1H} NMR (202 MHz, CD2Cl2): δ 24.2 (2P, PPh3). Anal Calc. for C63H52BBrF4N2P2Pd: C, 64.55; H, 4.47; N, 2.39. Found: C, 64.51; H, 4.44; N, 2.49. MS (ESI) m/z = 1085 [M - BF4]+. 6-Bromo-2-Methylbenzimidazole (12) H N Br Glacial acetic acid (3 mL) was added into a schlenk tube fitted with a reflux condenser containing 4-Bromo-1,2-diaminobenzene N (0.560 g, 3.0 mmol) under an atmosphere of nitrogen. The mixture was refluxed overnight under an inert atmosphere of nitrogen. The excess 53 acetic acid was then removed in vacuo and the residue was neutralized with a small amount of saturated K2CO3 solution. The mixture was then filtered and the residue was washed with water to yield 12 (0.510 g, 2.41 mmol, 81%) as a brown powder. Analytical data of this compound was identical with literature values.32 6-Bromo-1,3,-Dibenzyl-2-Methylbenzimidazolium Bromide (13) To a suspension of 12 (0.506 g, 2.4 mmol) in CH3CN (30 mL), NaOH (0.423 mL, 2.64 mmol, 6.25 M) was added. The resulting N Br N mixture was stirred for 30 minutes before benzyl bromide (0.285 - Br mL, 2.4 mmol) was added. The mixture was left to stir overnight at ambient temperature. After removing the volatiles and solvent in vacuo, the residue was suspended in H2O and the mixture was extracted with CH2Cl2 (3 x 25 mL). The combined organic extracts were washed with H2O (75 mL). The solvent was removed in vacuo, and the residue was redissolved in toluene (30 mL). Benzyl bromide (3.5 mL, 29.4 mmol) was added to this solution and the mixture was refluxed over 3 days. The brown precipitate formed was filtered off and washed with toluene to yield 13 (0.780 g, 1.65 mmol, 69%). 1H NMR (300 MHz, DMSO-d6): δ 8.33 (1H , Ar-H) 7.92 (d, 1H, Ar-H), 7.79 (d, 1H, Ar-H), 7.37 (br s, 10H, Ar-H), 5.83 (s, 4H, CH2), 2.98 (s, 3H, CH3). 13 C{1H} NMR (75.5 MHz, DMSO-d6): δ 153.6 (NCN), 133.8, 132.3, 130.4, 129.4, 129.0, 128.9, 128.4, 127.3, 127.2 (Ar-C), 118.8 (C-Br), 116.1, 115.2 (Ar-C), 48.5, 48.4 (CH2), 11.3 (CH3). Anal Calc. for C22H20Br2N2: C, 55.96; H, 4.27; N, 5.93. Found: C, 55.85; H, 4.21; N, 6.12. MS (ESI): m/z = 391 [M - Br]+ , 79 [Br]-. 54 6-Bromo-1,3,-Dibenzyl-2-Methylbenzimidazolium Tetrafluoroborate (14) 13 (0.472 g, 1.0 mmol) was dissolved in methanol (35 mL). NaBF4 (1.098 g, 10 mmol) was added to the solution and the N Br N mixture was stirred overnight at room temperature. The solvent BF4- was then removed in vacuo and CH2Cl2 was added to the reaction mixture. The suspension was filtered and the filtrate was collected. The solvent of the filtrate was removed under reduced pressure to yield 14 (0.293 g, 0.61 mmol, 61%). Crystals suitable for X-ray diffraction studies were obtained by the slow evaporation of a concentrated solution of 14 in methanol. 1H NMR (300 MHz, CD2Cl2): δ 7.77 (s, 1H, Ar-H), 7.66-7.62 (m, 1H, Ar-H), 7.53-7.50 (m, 1H, Ar-H), 7.37-7.36 (m, 6H, Ar-H), 7.22-7.18 (m, 4H, Ar-H), 5.63, 5.61 (s, 4H, CH2), 2.87 (s, 3H, CH3). 13 C{1H} NMR (76 MHz, CD2Cl2): δ153.1 (NCN), 132.7, 132.7, 132.5, 130.9, 130.8, 129.8, 129.7, 127.1, 127.0 (Ar-C), 120.7 (C-Br), 116.2, 114.8 (Ar-C), 49.9, 49.8 (CH2), 11.5 (CH3). 19F{1H} NMR (282.4 MHz, CD2Cl2): δ 76.74 (s, 10BF4), -76.79 (s, 11BF4). Anal Calc. for C22H20BBrF4N2: C, 55.15; H, 4.21; N, 5.85. Found : C, 55.44; H, 4.22; N, 5.79. MS (ESI): m/z = 391 [M - BF4]+, 87 [BF4]-. 55 [PdBr(Bn2-2Me-bim)(PPh3)2]+BF4- (15) 14 (0.095 g, 0.2 mmol) and [Pd(PPh3)4] (0.230 g, 0.2 mmol) was added into a two neck rbf fitted with a reflux N Ph3 P Pd Br PPh3 N condenser under an atmosphere of nitrogen. Anhydrous BF 4- CH2Cl2 (10 mL) was added into the flask and the reaction mixture was refluxed under nitrogen overnight shielded from light. The reaction mixture was then concentrated down to a few mL, and added dropwise into a rbf of diethyl ether (100 mL) with vigorous stirring. The precipitate formed was filtered and washed with diethyl ether (2 x 50 mL). THF (15 mL) was added to the precipitate and the solution was left to stand for a few minutes. The white precipitate formed upon standing was collected and washed with small amounts of THF to yield 15 (0.180 g, 0.16 mmol, 80%). 1H NMR (300 MHz, CD2Cl2): δ 7.477.31 (m, 21H, Ar-H), 7.23-7.18 (Ar-H, 15H, Ar-H), 7.09-7.06 (m, 2H, Ar-H), 6.986.92 (m, 3H, Ar-H), 6.70 (s, 1H, Ar-H), 6.51-6.48 (m, 1H, Ar-H), 5.35 (s, 2H, CH2), 5.06 (s, 2H, CH2), 2.78 (s, 3H, CH3). 2 13 C{1H} NMR (76 MHz, CD2Cl2): δ 159.5 (t, J(P,C) = 4.42 Hz, C-Pd), 147.8 (NCN), 134.9 (2/3J(P,C) = 6.36 Hz, Ar-C), 133.4 (s, Ar-C), 133.2 (s, Ar-C), 131.0 (t, 1J(P,C) = 23.8, Ar-C), 130.6 (s, Ar-C), 129.6 (s, ArC), 129.5 (s, Ar-C), 129.3 (s, Ar-C), 129.2 (s,Ar-C), 128.3 (t, 2/3J(P,C) = 5.25 Hz, ArC), 127.2 (s, Ar-C), 127.1 (s, Ar-C), 118.5 (t, 2/3J(P,C) = 5.80 Hz, Ar-C), 110.4 (s, ArC), 49.0 (s, CH2), 48.9 (s, CH2), 11.1 (s, CH3). 19F{1H} NMR (282.4 MHz, CD2Cl2): δ -76.64 (s, 10 BF4), -76.68 (s, 11 BF4). 31 P{1H} NMR (121 MHz, CD2Cl2): δ 25.1 (s, 2P, PPh3). Anal Calc. for C58H50BBrF4N2P2Pd: C, 62.75; H, 4.54; N, 2.52. Found: C, 62.89; H, 4.49; N, 2.59. MS (ESI): m/z = 1023 [M - BF4]+, 761 [M - BF4 - PPh3]+. 56 Bromo(4-formylphenyl)bis(triphenylphosphine)palladium(II) (16c) O Ph3P Br The Synthesis of compound 16c is known.24 However, spectroscopic data was not reported. 1H NMR (300 MHz, CDCl3): Pd PPh3 δ 9.56 (s, 1H, CHO), 7.58-7.54 (m, 13H, Ar-C), 7.39-7.28 (m, 17H, Ar-C), 6.97-6.94 (m, 2H, Ar-C), 6.71-6.68 (m, 2H, Ar-C). 13 C{1H} NMR (76 MHz, CDCl3): δ 193.4 (s, CHO), 174.3 (t, 2J(P,C) = 6.36 Hz, C-Pd), 137.3 (t, 2/3 J(P,C) = 8.25 Hz, Ar-C), 135.3 (t, 2/3J(P,C) = 10.54 Hz, Ar-C), 131.56 (t, 1J(P,C) = 38.95 Hz, Ar-C), 130.7 (s, Ar-C), 128.6 (t, 2/3 J(P,C) = 8.71 Hz, Ar-C), 128.2 (s, Ar- C). 31P{1H} NMR (121 MHz, CDCl3): δ 24.2 (s, 2P, PPh3). General Procedure for the Buchwald-Hartwing Amination Reaction In a typical run, a schlenk tube was charged with a mixture of 15 (1 mol%), KOtBu (1.5 mmol), degassed DME (2 mL), 3- bromopyridine (1 mmol) and morpholine (1.2 mmol) under an inert atmosphere of nitrogen. The reaction mixture was then stirred at 50 °C for 24 h unless otherwise indicated. The reaction mixture was cooled and water (15 mL) was added to the reaction mixture. The mixture was extracted with CH2Cl2 (3 x 15 mL). The solvent of organic extracts was removed in vacuo, and the product was purified by column chromatography using ethyl acetate as the eluant. General Procedure for the Sonogashira Coupling Reaction In a typical run, a schlenk tube was charged with a mixture of degassed DMF (1 mL), CuI (5 mol%), aryl halide (1 mmol, 1 equiv), phenylacetylene (2 mmol, 2 equiv) triethylamine (1.2 mmol, 1.2 equiv) and 15 (1 mol%) under an inert atmosphere of 57 nitrogen. The reaction mixture was then stirred at 80 °C for 24 h unless otherwise indicated. The reaction mixture was cooled and CH2Cl2 (15 mL) was added to the reaction mixture. The mixture was washed with water (3 x 20 mL). The solvent was allowed to evaporate and the residue was analyzed by 1H NMR spectroscopy. 2-({4-phenylacetylenyl}phenyl)-1-Ethylbenzimidazole (17) N 1 N 1H, Ar-H), 7.76-7.68 (m, 4H, Ar-H), 7.59-7.55 H NMR (300 MHz, CDCl3): δ 7.86-7.83 (m, (m, 2H, Ar-H), 7.45-7.31 (m, 6H, Ar-H), 4.32 (q, 3 J(H,H) = 6.9 Hz, 2H, CH2), 1.49 (t, 3J(H,H) = 6.9 Hz, 3H, CH3). 13C{1H} NMR (76 MHz, CDCl3): δ 153.3 (NCN), 143.9, 136.1, 132.5, 132.4, 131.4, 130.8, 129.8, 129.3, 129.1, 125.5, 123.6, 123.2, 120.7, 110.6 (Ar-C), 92.0, 89.4 (C≡C), 40.4 (CH2), 15.9 (CH3). Anal Calc. for C23H18N2: C, 85.68; H, 5.63; N, 8.69. Found: C, 83.12; H, 5.60; N, 8.33. MS (ESI): m/z = 323 [M + H]+. X-ray Diffraction Studies X-ray data were collected with a Bruker AXS SMART APEX diffractometer, using Mo Kα radiation at 100 K (9·4CH3OH and 15), 223 K (10·½C4H10O, 11·3CH3OH and 14) or 295 K (6), with the SMART suite of Programs.33 Data were processed and corrected for Lorentz and polarisation effects with SAINT,34 and for absorption effect with SADABS.35 Structural solution and refinement were carried out with the SHELXTL suite of programs.36 The structure was solved by direct methods to locate the heavy atoms, followed by difference maps for the light, non-hydrogen atoms. All 58 hydrogen atoms were put at calculated positions. All non-hydrogen atoms were generally given anisotropic displacement parameters in the final model. A summary of the most important crystallographic data is given in Appendix 1. 59 Appendix 1: Selected Crystallographic Data formula formula weight colour, habit cryst size [mm] temp [K] cryst syst space group a [Å] b [Å] c [Å] α [deg] β [deg] γ [deg] V [Å3] Z Dc [g cm-3] μ [mm-1] θ range [deg] Reflections collected Independent reflections max., min. transmn final R indices [I>2σ(I)] R indices (all data) goodness-of-fit on F2 peak/hole [e Å-3] 6 C17H18BBrF4N2 417.05 colourless, block 0.46 x 0.25 x 0.10 295(2) monoclinic P2(1)/n 18.0888(7) 8.7251(3) 23.6914(9) 90 104.4050(10) 90 3621.6(2) 8 1.530 2.310 1.27-27.48 8296 4492 0.8019, 0.4163 R1 = 0.0664 wR2 = 0.1946 R1 = 0.1166 wR2 = 0.2253 1.016 0.816 / -0.532 9·4CH3OH C56H63BBrF4N2O4.5P2Pd 1171.14 colourless, block 0.24 x 0.14 x 0.10 100(2) orthorhombic Pbca 23.3870(14) 17.8646(11) 28.1841(17) 90 90 90 11775.3(12) 8 1.321 1.105 1.45-27.50 13503 8831 0.8975, 0.7774 R1 = 0.0685 wR2 = 0.1726 R1 = 0.1124 wR2 = 0.1914 1.053 0.966 / -0.850 10·½C4H10O C60H55BBrF4N2O0.5P2Pd 1147.12 colourless, needle 0.40 x 0.26 x 0.08 223(2) monoclinic C2/c 23.7448(11) 27.3664(12) 18.2796(8) 90 95.6040(10) 90 11821.5(9) 8 1.289 1.094 1.14-25.00 10426 7266 0.9175, 0.6686 R1 = 0.0754 wR2 = 0.2243 R1 = 0.1041 wR2 = 0.2436 1.060 1.673 / -0.973 11·3CH3OH C66H64BBrF4N2O3 P2Pd 1268.25 yellow, block 0.30 x 0.26 x 0.12 223(2) monoclinic P2(1)/n 14.2471(6) 18.3758(9) 23.1710(10) 90 96.5290(10) 90 6026.9(5) 4 1.398 1.084 1.60-27.50 13820 9022 0.8810, 0.7369 R1 = 0.0630 wR2 = 0.1520 R1 = 0.1045 wR2 = 0.1706 1.020 1.480 / -0.911 60 formula formula weight colour, habit cryst size [mm] temp [K] cryst syst space group a [Å] b [Å] c [Å] α [deg] β [deg] γ [deg] V [Å3] Z Dc [g cm-3] μ [mm-1] θ range [deg] Reflections collected Independent reflections max., min. transmn final R indices [I>2σ(I)] R indices (all data) goodness-of-fit on F2 peak/hole [e Å-3] 14 C22H20BBrF4N2 479.12 thin plate, colourless 0.22 x 0.17 x 0.06 223(2) triclinic P-1 9.834(2) 10.713(3) 11.724(3) 81.420(4) 67.166(3) 70.022(3) 1069.7(4) 2 1.487 1.966 1.88-25.00 3759 2272 0.8911, 0.6716 R1 = 0.0719 wR2 = 0.173 R1 = 0.1235 wR2 = 0.2005 1.032 0.526 / -0.432 15 C58H50BBrF4N2P2Pd 1110.06 rod, colourless 0.50 x 0.34 x 0.30 100(2) monoclinic P2(1)/c 12.4554(10) 13.9046(11) 29.570(2) 90 100.219(2) 90 5040.0(7) 4 1.463 1.280 1.40-25.00 8875 5280 0.7000, 0.5670 R1 = 0.0992 wR2 = 0.1947 R1 = 0.1664 wR2 = 0.2226 1.036 3.463 / -1.577 61 References 1. Reviews: (a) Hahn, F. E.; Jahnke, M. C. Angew. Chem. Int. Ed. 2008, 47, 3122; (b) Bourissou, D.; Guerret, O.; Gabbaï, F. P.; Bertrand, G. Chem. Rev. 2000, 200, 39. 2. Schuster, G. B.; Adv. Phys. Org, Chem. 1986, 22, 311. 3. Hoffmann, R.; Zeiss, G. D.; Van Dine, G. W. J. Am. Chem. Soc. 1991, 22, 311. 4. Fischer, E. O.; Maasbol, A. Angew. Chem. Int. Ed. 1964, 3, 580. 5. Schrock, R. R. J. Am. Chem. Soc. 1974, 96, 6796. 6. Wanzlick, H. W Angew. Chem. Int Ed. 1962, 2, 75. 7. Wanzlick, H. W.; Schönherr, H. J Angew. Chem. Int Ed. 1968, 2, 141. 8. Arduengo, A. J.; Harlow, R. L.; Kline, M. J. J. Am. Chem. Soc. 1991, 113, 361. 9. (a) Herrmann, W. A.; Öfele, K.; Elison, M.; Kühn, F. E.; Roesky, P. W. J. Organomet. Chem 1994, 480, C7; (b) Huang, J. K.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am. Chem. Soc. 1999, 121, 2674; (c) Perrin, L.; Clot, E.; Eisenstein, O.; Loch, J.; Crabtree, R. H. Inorg. Chem.2001, 40, 5806. 10. (a) Albrecht, M. Chem. Commun. 2008, 3601. (b) Jothibasu, R.; Huynh, H. V. Organometallics 2009, 28, 2505-2511. 11. (a) Raubenheimer, H. G.; Cronje, S. Dalton Trans. 2008, 1265. (b) Han, Y.; Huynh, H. V. Organometallics 2007, 26, 6581. 12. Heckenroth, M.; Kluser, E.; Neels, A.; Albrecht, M. Angew. Chem. Int. Ed. 2007, 46, 6293. 13. Wang, H. M. J.; Lin, I. J. B. Organometallics 1998, 17, 972. 62 14. Chianese, A. R.; Kovacevic, A.; Zeglis, B. M.; Faller, J. W.; Crabtree, R. H. Organometallics 2004, 23, 2461. 15. (a) Fraser, P. J.; Roper, W. R.; Stone, F. G. A. J. Am. Chem. Soc. 1973, 50, C54. (b) Fraser, P. J.; Roper, W. R.; Stone, F. G. A. Dalton Trans. 1974, 102. 16. (a) Kluser, E.; Neels, A.; Albrecht, M. Chem Commun. 2006, 4495.; (b) Han, Y.; Huynh, H. V.; Chem. Commun. 2007, 1089; (c) Han, Y.; Huynh, H. V. Organometallics 2007, 26, 6581; (d) Schneider, S. K.; Julius, G. R.; Loschen, C.; Raubenheimer, H. G.; Frenking, G.; Herrmann, W. A. Dalton Trans. 2006, 1226. 17. Schuster, O.; Raubenheimer, H. G. Inorg. Chem. 2006, 45, 7997. 18. Aumann, R.; Jasper, B.; Froehlich, R. Organometallics 1995, 14, 2447. 19. K. Bahrami, M. M. Khodaei, I. Kavianinia, Synthesis, 2007, 4, 547. 20. Daniel, R. B.; de Visser, S. P.; Shaik, S.; Neumann, R. J. Am. Chem. Soc. 2003, 125, 12116. 21. Huynh, H. V.; Wong, L. R.; Ng, P. S. Organometallics 2008, 27, 2231. 22. Schuster, O.; Yang, L.; Raubneheimer, H. G.; Albrecht, M. Chem. Rev. 2009, 109, 3445. 23. Bruno, I. J.; Cole, J.C.; Edgington, P. R.; Kessler, M.; Macrae, C.F.; McCabe, P.; Pearson, J.; Taylor, R. Acta Crystallogr. 2002, B58, 389-397. 24. Tam, W.; Calabrese, J. C. Chem. Phys. Lett. 1988, 144, 79. 25. (a) Yang, B. H.; Buchwald, S. L. J. Organomet. Chem. 1999, 576, 125; (b) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046; (c) Modern Amination Methods (Ed.: Ricci, A.), Wiley-VCH, Weinheim, 2000; (d) Prim, D.; Campagne, J.-M.; Joseph, D.; Andrioletti, B. Tetrahedron 2002, 58, 2041. 63 26. (a) Kantchev, E. A.; O’Brien, C. J.; Organ, M. G. Angew. Chem. Int. Ed. 2007, 46, 2768; (b) Kremzow, D.; Seidel, G.; Lehmann, C. W.; Fürstner, A. Chem. Eur. J. 2005, 11, 1833. 27. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron letters 1975, 50, 4467; (b) Doucet, H.; Hierso, J.-C. Angew. Chem. Int. Ed 2007, 46, 834; (c) Chinchilla, R.; Nájera, C. Chem. Rev. 2007, 107, 874. 28. Köllhofer, A.; Plenio, H. Adv. Synth. Catal. 2005, 347, 1295. 29. Hierso, J.-C. ; Fihri, A.; Amardeil, R.; Meunier, P.; Doucet, H. ; Santelli, M. ; Ivanov, V. V. Org. Lett. 2004, 6, 3473. 30. Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Org. Biomol. Chem. 2003, 1, 2235. 31. Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A. Heterocycles 2004, 63, 2769. 32. Treu, M.; Karner, T.; Kousek, R.; Berger, H.; Mayer, M.; McConnell, D. B.; Stadler, A. J. Comb. Chem. 2008, 10, 863. 33. SMART version 5.628; Bruker AXS Inc.: Madison, WI, USA, 2001. 34. SAINT+ version 6.22a; Bruker AXS Inc.: Madison, WI, USA, 2001. 35. Sheldrick, G. W. SADABS version 2.10; University of Göttingen, 2001. 36. SHELXTL version 6.14; Bruker AXS Inc.: Madison, WI, USA, 2000. 37. Barhate, N. B.; Gajare, A. S.; Wakharkar, R. D.; Bedekat, A. V. Tetrahedron Lett. 1998, 39, 6349. 64 [...]... N E Figure 1.9 Examples of remote carbenes Experimental and theoretical studies have shown that carbene ligands with less heteroatomic stabilization are not only more donating than classical NHCs, but also show better activity in certain catalytic reactions.10 9 1.5 Synthesis of Non- Classical N-Heterocyclic Carbenes With the rising interests in non- classical NHC chemistry, a number of known methods... states Schrock carbenes are nucleophillic, and are in the singlet state Ta Figure 1.4 The first example of a Schrock Carbene 1.3 Classical N-Heterocyclic Carbenes A special class of Fischer carbene that has caught much attention lately is the Nheterocyclic carbene (NHC) In NHCs, the carbene carbon atom is incorporated into a heterocyclic ring The classical representation of this type of ligands describes... orbital (σ2pπ0 and σ0pπ2) and an excited singlet state (1B1) with antiparallel occupation of the σ and p orbitals (σ1pπ1).1 1 py linear px p 3 B1( p p bent 1 A1( p Figure 1.1 Frontier orbitals and possible electronic configurations for carbene carbon atoms1a Figure 1.2 Electronic configurations of sp2-hybridized carbenes The reactivity and properties of carbenes are fundamentally determined by their ground-state... carbon donor atom would be 5 bonds away from the heteroatoms and the ring containing the carbene carbon and the heterocycle are only connected by one C-C bond A structural analysis of the ligand’s geometry in the metal complex can draw distinction on whether the ligand acts as a zwitterionic ligand (Scheme 1.8, B) or a neutral carbene In the carbene form, the system should be conjugated with alternating... that there are two phosphine ligands to one carbon donor ligand The phosphine donors in all three complexes resonate as singlets at similar positions in the 31 P NMR spectra with chemical shifts of 24.3 ppm (9, 10) and 24.2 ppm (11) each, indicating a trans arrangement of the phosphine ligands In their 13C NMR spectra, the disappearance of a signal at ca 119 ppm (C-Br) and the appearance of a triplet... increment in the energy gap between the σ and pπ orbitals, thus stabilizing the singlet carbene Figure 1.6 shows a pictorial representation of the electronic interactions and their resonance structures Scheme 1.2 Arduengo’s synthesis of the first stable NHC Arduengo’s discovery sparked interest in NHC chemistry, and as a result rapid development in the syntheses and applications of NHCs followed In particular,... (Scheme 1.8, A) On the other hand, if the ligand acts as a zwitterionic aryl ligand, the C-C bond between the two rings would have free rotation, resulting in a non- linear geometry of the ligand due to steric repulsion between the two rings The results and details of this study will be discussed in Chapter 2 R N L M X L N R A R N L M X L N R B Scheme 1.9 The proposed R2-2Ph-bim ligand system A second system,... six valence electrons A carbene can be described as an organic molecule with the general formula RR’C:, in which the carbene carbon atom contains a pair of nonbonding electrons and is covalently bonded to two other atoms Depending on the degree of hybridization, the geometry at the carbene carbon atom can either be bent or linear When a carbene centre is sp-hybridized with two nonbonding energetically... generation Grubb’s catalyst with a 7 NHC ligand led to a significant improvement in the stability of the catalyst for olefin metathesis reactions N Cl Cl N Ru Ph PCy3 Figure 1.7 The Second generation Grubb’s catalyst 1.4 Non- Classical N-Heterocyclic Carbenes While most research on the topic of NHCs has been centered on the Arduengotype carbenes, where the carbene carbon atom is stabilized by two adjacent... abnormal NHC On the other hand, remote NHCs refer to carbenes which are stabilized by remote heteroatoms This class of carbenes differ from the classical NHCs since they contain no heteroatom at the position α to the carbene centre In this case, the heteroatom can be located within the same ring as the carbenoid carbon (Figure 1.9, A-C) or in an adjacent ring (Figure 1.9, D and E).11 N A B N C D N E ... of Carbenes 1.2 Carbenes as Ligands in Metal Complexes 1.3 Classical N-Heterocyclic Carbenes 1.4 Non- classical N-Heterocyclic Carbenes 1.5 Synthesis of Non- classical N-Heterocyclic Carbenes... than classical NHCs, but also show better activity in certain catalytic reactions.10 1.5 Synthesis of Non- Classical N-Heterocyclic Carbenes With the rising interests in non- classical NHC chemistry, ... Schrock carbenes are nucleophillic, and are in the singlet state Ta Figure 1.4 The first example of a Schrock Carbene 1.3 Classical N-Heterocyclic Carbenes A special class of Fischer carbene